AnatomyOrganismsDiseasesChemicals and DrugsAnalytical, Diagnostic and Therapeutic Techniques and EquipmentPsychiatry and PsychologyPhenomena and ProcessesInformation Science
Amyloid beta-Protein PrecursorAmyloid beta-PeptidesAmyloidAlzheimer DiseaseProtein PrecursorsPeptide FragmentsAmyloid Precursor Protein SecretasesSmilacaceaePlaque, AmyloidCerebral Amyloid AngiopathyAspartic Acid EndopeptidasesAmyloid NeuropathiesMoraceaeEndopeptidasesBrainIridoid GlycosidesMolecular Sequence DataAmino Acid SequenceSerum Amyloid A ProteinNeuronsMice, TransgenicCell LineCells, CulturedCerebral CortexProtein Processing, Post-TranslationalAmyloidosisDisease Models, AnimalIslet Amyloid PolypeptideBase SequenceAgingInterleukin-1betaRNA, MessengerPresenilin-1Serum Amyloid P-ComponentMutationCongo RedInsulysinRecombinant ProteinsCloning, MolecularVitellogeninsKineticsS100 Calcium Binding Protein beta SubunitVitellogenesisPeptidesbeta 2-MicroglobulinTransfectionPresenilin-2ThiazolesBlotting, Westerntau ProteinsNeurofibrillary TanglesMembrane Proteins
Amyloid beta-Protein Precursor
A single-pass type I membrane protein. It is cleaved by AMYLOID PRECURSOR PROTEIN SECRETASES to produce peptides of varying amino acid lengths. A 39-42 amino acid peptide, AMYLOID BETA-PEPTIDES is a principal component of the extracellular amyloid in SENILE PLAQUES.
Amyloid beta-Peptides
Peptides generated from AMYLOID BETA-PEPTIDES PRECURSOR. An amyloid fibrillar form of these peptides is the major component of amyloid plaques found in individuals with Alzheimer's disease and in aged individuals with trisomy 21 (DOWN SYNDROME). The peptide is found predominantly in the nervous system, but there have been reports of its presence in non-neural tissue.
Amyloid
A fibrous protein complex that consists of proteins folded into a specific cross beta-pleated sheet structure. This fibrillar structure has been found as an alternative folding pattern for a variety of functional proteins. Deposits of amyloid in the form of AMYLOID PLAQUES are associated with a variety of degenerative diseases. The amyloid structure has also been found in a number of functional proteins that are unrelated to disease.
Alzheimer Disease
A degenerative disease of the BRAIN characterized by the insidious onset of DEMENTIA. Impairment of MEMORY, judgment, attention span, and problem solving skills are followed by severe APRAXIAS and a global loss of cognitive abilities. The condition primarily occurs after age 60, and is marked pathologically by severe cortical atrophy and the triad of SENILE PLAQUES; NEUROFIBRILLARY TANGLES; and NEUROPIL THREADS. (From Adams et al., Principles of Neurology, 6th ed, pp1049-57)
Protein Precursors
Peptide Fragments
Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.
Amyloid Precursor Protein Secretases
Endopeptidases that are specific for AMYLOID PROTEIN PRECURSOR. Three secretase subtypes referred to as alpha, beta, and gamma have been identified based upon the region of amyloid protein precursor they cleave.
Smilacaceae
A plant family of the order Liliales, subclass Liliidae, class Liliopsida (monocotyledon).
Plaque, Amyloid
Accumulations of extracellularly deposited AMYLOID FIBRILS within tissues.
Cerebral Amyloid Angiopathy
A heterogeneous group of sporadic or familial disorders characterized by AMYLOID deposits in the walls of small and medium sized blood vessels of CEREBRAL CORTEX and MENINGES. Clinical features include multiple, small lobar CEREBRAL HEMORRHAGE; cerebral ischemia (BRAIN ISCHEMIA); and CEREBRAL INFARCTION. Cerebral amyloid angiopathy is unrelated to generalized AMYLOIDOSIS. Amyloidogenic peptides in this condition are nearly always the same ones found in ALZHEIMER DISEASE. (from Kumar: Robbins and Cotran: Pathologic Basis of Disease, 7th ed., 2005)
Aspartic Acid Endopeptidases
A sub-subclass of endopeptidases that depend on an ASPARTIC ACID residue for their activity.
Amyloid Neuropathies
Disorders of the peripheral nervous system associated with the deposition of AMYLOID in nerve tissue. Familial, primary (nonfamilial), and secondary forms have been described. Some familial subtypes demonstrate an autosomal dominant pattern of inheritance. Clinical manifestations include sensory loss, mild weakness, autonomic dysfunction, and CARPAL TUNNEL SYNDROME. (Adams et al., Principles of Neurology, 6th ed, p1349)
Moraceae
The mulberry plant family of the order Urticales, subclass Hamamelidae, class Magnoliopsida. They have milky latex and small, petalless male or female flowers.
Endopeptidases
A subclass of PEPTIDE HYDROLASES that catalyze the internal cleavage of PEPTIDES or PROTEINS.
Brain
The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM.
Iridoid Glycosides
A subclass of iridoid compounds that include a glycoside moiety, usually found at the C-1 position.
Molecular Sequence Data
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
Amino Acid Sequence
The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.
Serum Amyloid A Protein
An ACUTE PHASE REACTION protein present in low concentrations in normal sera, but found at higher concentrations in sera of older persons and in patients with AMYLOIDOSIS. It is the circulating precusor of amyloid A protein, which is found deposited in AA type AMYLOID FIBRILS.
Neurons
The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM.
Mice, Transgenic
Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.
Cell Line
Established cell cultures that have the potential to propagate indefinitely.
Cells, Cultured
Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.
Cerebral Cortex
The thin layer of GRAY MATTER on the surface of the CEREBRAL HEMISPHERES that develops from the TELENCEPHALON and folds into gyri and sulchi. It reaches its highest development in humans and is responsible for intellectual faculties and higher mental functions.
Protein Processing, Post-Translational
Any of various enzymatically catalyzed post-translational modifications of PEPTIDES or PROTEINS in the cell of origin. These modifications include carboxylation; HYDROXYLATION; ACETYLATION; PHOSPHORYLATION; METHYLATION; GLYCOSYLATION; ubiquitination; oxidation; proteolysis; and crosslinking and result in changes in molecular weight and electrophoretic motility.
Amyloidosis
A group of sporadic, familial and/or inherited, degenerative, and infectious disease processes, linked by the common theme of abnormal protein folding and deposition of AMYLOID. As the amyloid deposits enlarge they displace normal tissue structures, causing disruption of function. Various signs and symptoms depend on the location and size of the deposits.
Disease Models, Animal
Naturally occurring or experimentally induced animal diseases with pathological processes sufficiently similar to those of human diseases. They are used as study models for human diseases.
Islet Amyloid Polypeptide
A pancreatic beta-cell hormone that is co-secreted with INSULIN. It displays an anorectic effect on nutrient metabolism by inhibiting gastric acid secretion, gastric emptying and postprandial GLUCAGON secretion. Islet amyloid polypeptide can fold into AMYLOID FIBRILS that have been found as a major constituent of pancreatic AMYLOID DEPOSITS.
Base Sequence
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
Aging
The gradual irreversible changes in structure and function of an organism that occur as a result of the passage of time.
Interleukin-1beta
An interleukin-1 subtype that is synthesized as an inactive membrane-bound pro-protein. Proteolytic processing of the precursor form by CASPASE 1 results in release of the active form of interleukin-1beta from the membrane.
RNA, Messenger
RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.
Presenilin-1
Integral membrane protein of Golgi and endoplasmic reticulum. Its homodimer is an essential component of the gamma-secretase complex that catalyzes the cleavage of membrane proteins such as NOTCH RECEPTORS and AMYLOID BETA-PEPTIDES precursors. PSEN1 mutations cause early-onset ALZHEIMER DISEASE type 3 that may occur as early as 30 years of age in humans.
Serum Amyloid P-Component
Amyloid P component is a small, non-fibrillar glycoprotein found in normal serum and in all amyloid deposits. It has a pentagonal (pentaxin) structure. It is an acute phase protein, modulates immunologic responses, inhibits ELASTASE, and has been suggested as an indicator of LIVER DISEASE.
Mutation
Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.
Congo Red
An acid dye used in testing for hydrochloric acid in gastric contents. It is also used histologically to test for AMYLOIDOSIS.
Insulysin
An enzyme the catalyzes the degradation of insulin, glucagon and other polypeptides. It is inhibited by bacitracin, chelating agents EDTA and 1,10-phenanthroline, and by thiol-blocking reagents such as N-ethylmaleimide, but not phosphoramidon. (Eur J Biochem 1994;223:1-5) EC 3.4.24.56.
Recombinant Proteins
Proteins prepared by recombinant DNA technology.
Cloning, Molecular
The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells.
Vitellogenins
Phospholipoglycoproteins produced in the fat body of egg-laying animals such as non-mammalian VERTEBRATES; ARTHROPODS; and others. Vitellogenins are secreted into the HEMOLYMPH, and taken into the OOCYTES by receptor-mediated ENDOCYTOSIS to form the major yolk proteins, VITELLINS. Vitellogenin production is under the regulation of steroid hormones, such as ESTRADIOL and JUVENILE HORMONES in insects.
Kinetics
The rate dynamics in chemical or physical systems.
S100 Calcium Binding Protein beta Subunit
A calcium-binding protein that is 92 AA long, contains 2 EF-hand domains, and is concentrated mainly in GLIAL CELLS. Elevation of S100B levels in brain tissue correlates with a role in neurological disorders.
Vitellogenesis
The active production and accumulation of VITELLINS (egg yolk proteins) in the non-mammalian OOCYTES from circulating precursors, VITELLOGENINS. Vitellogenesis usually begins after the first MEIOSIS and is regulated by estrogenic hormones.
Peptides
Members of the class of compounds composed of AMINO ACIDS joined together by peptide bonds between adjacent amino acids into linear, branched or cyclical structures. OLIGOPEPTIDES are composed of approximately 2-12 amino acids. Polypeptides are composed of approximately 13 or more amino acids. PROTEINS are linear polypeptides that are normally synthesized on RIBOSOMES.
beta 2-Microglobulin
An 11-kDa protein associated with the outer membrane of many cells including lymphocytes. It is the small subunit of the MHC class I molecule. Association with beta 2-microglobulin is generally required for the transport of class I heavy chains from the endoplasmic reticulum to the cell surface. Beta 2-microglobulin is present in small amounts in serum, csf, and urine of normal people, and to a much greater degree in the urine and plasma of patients with tubular proteinemia, renal failure, or kidney transplants.
Transfection
The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.
Presenilin-2
Integral membrane protein of Golgi and endoplasmic reticulum. Its homodimer is an essential component of the gamma-secretase complex that catalyzes the cleavage of membrane proteins such as NOTCH RECEPTORS and AMYLOID BETA-PEPTIDES precursors. PSEN2 mutations cause ALZHEIMER DISEASE type 4.
Thiazoles
Blotting, Western
Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.
tau Proteins
Microtubule-associated proteins that are mainly expressed in neurons. Tau proteins constitute several isoforms and play an important role in the assembly of tubulin monomers into microtubules and in maintaining the cytoskeleton and axonal transport. Aggregation of specific sets of tau proteins in filamentous inclusions is the common feature of intraneuronal and glial fibrillar lesions (NEUROFIBRILLARY TANGLES; NEUROPIL THREADS) in numerous neurodegenerative disorders (ALZHEIMER DISEASE; TAUOPATHIES).
Neurofibrillary Tangles
Abnormal structures located in various parts of the brain and composed of dense arrays of paired helical filaments (neurofilaments and microtubules). These double helical stacks of transverse subunits are twisted into left-handed ribbon-like filaments that likely incorporate the following proteins: (1) the intermediate filaments: medium- and high-molecular-weight neurofilaments; (2) the microtubule-associated proteins map-2 and tau; (3) actin; and (4) UBIQUITINS. As one of the hallmarks of ALZHEIMER DISEASE, the neurofibrillary tangles eventually occupy the whole of the cytoplasm in certain classes of cell in the neocortex, hippocampus, brain stem, and diencephalon. The number of these tangles, as seen in post mortem histology, correlates with the degree of dementia during life. Some studies suggest that tangle antigens leak into the systemic circulation both in the course of normal aging and in cases of Alzheimer disease.
Membrane Proteins
Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.

The amyloid precursor protein interacts with Go heterotrimeric protein within a cell compartment specialized in signal transduction. (1/2953)

The function of the beta-amyloid protein precursor (betaAPP), a transmembrane molecule involved in Alzheimer pathologies, is poorly understood. We recently reported the presence of a fraction of betaAPP in cholesterol and sphingoglycolipid-enriched microdomains (CSEM), a caveolae-like compartment specialized in signal transduction. To investigate whether betaAPP actually interferes with cell signaling, we reexamined the interaction between betaAPP and Go GTPase. In strong contrast with results obtained with reconstituted phospholipid vesicles (Okamoto et al., 1995), we find that incubating total neuronal membranes with 22C11, an antibody that recognizes an N-terminal betaAPP epitope, reduces high-affinity Go GTPase activity. This inhibition is specific of Galphao and is reproduced, in the absence of 22C11, by the addition of the betaAPP C-terminal domain but not by two distinct mutated betaAPP C-terminal domains that do not bind Galphao. This inhibition of Galphao GTPase activity by either 22C11 or wild-type betaAPP cytoplasmic domain suggests that intracellular interactions between betaAPP and Galphao could be regulated by extracellular signals. To verify whether this interaction is preserved in CSEM, we first used biochemical, immunocytochemical, and ultrastructural techniques to unambiguously confirm the colocalization of Galphao and betaAPP in CSEM. We show that inhibition of basal Galphao GTPase activity also occurs within CSEM and correlates with the coimmunoprecipitation of Galphao and betaAPP. The regulation of Galphao GTPase activity by betaAPP in a compartment specialized in signaling may have important consequences for our understanding of the physiopathological functions of betaAPP.  (+info)

Proteolytic processing of the Alzheimer's disease amyloid precursor protein within its cytoplasmic domain by caspase-like proteases. (2/2953)

Alzheimer's disease is characterized by neurodegeneration and deposition of betaA4, a peptide that is proteolytically released from the amyloid precursor protein (APP). Missense mutations in the genes coding for APP and for the polytopic membrane proteins presenilin (PS) 1 and PS2 have been linked to familial forms of early-onset Alzheimer's disease. Overexpression of presenilins, especially that of PS2, induces increased susceptibility for apoptosis that is even more pronounced in cells expressing presenilin mutants. Additionally, presenilins themselves are targets for activated caspases in apoptotic cells. When we analyzed APP in COS-7 cells overexpressing PS2, we observed proteolytic processing close to the APP carboxyl terminus. Proteolytic conversion was increased in the presence of PS2-I, which encodes one of the known PS2 pathogenic mutations. The same proteolytic processing occurred in cells treated with chemical inducers of apoptosis, suggesting a participation of activated caspases in the carboxyl-terminal truncation of APP. This was confirmed by showing that specific caspase inhibitors blocked the apoptotic conversion of APP. Sequence analysis of the APP cytosolic domain revealed a consensus motif for group III caspases ((IVL)ExD). Mutation of the corresponding Asp664 residue abolished cleavage, thereby identifying APP as a target molecule for caspase-like proteases in the pathways of programmed cellular death.  (+info)

Translation of the alzheimer amyloid precursor protein mRNA is up-regulated by interleukin-1 through 5'-untranslated region sequences. (3/2953)

The amyloid precursor protein (APP) has been associated with Alzheimer's disease (AD) because APP is processed into the beta-peptide that accumulates in amyloid plaques, and APP gene mutations can cause early onset AD. Inflammation is also associated with AD as exemplified by increased expression of interleukin-1 (IL-1) in microglia in affected areas of the AD brain. Here we demonstrate that IL-1alpha and IL-1beta increase APP synthesis by up to 6-fold in primary human astrocytes and by 15-fold in human astrocytoma cells without changing the steady-state levels of APP mRNA. A 90-nucleotide sequence in the APP gene 5'-untranslated region (5'-UTR) conferred translational regulation by IL-1alpha and IL-1beta to a chloramphenicol acetyltransferase (CAT) reporter gene. Steady-state levels of transfected APP(5'-UTR)/CAT mRNAs were unchanged, whereas both base-line and IL-1-dependent CAT protein synthesis were increased. This APP mRNA translational enhancer maps from +55 to +144 nucleotides from the 5'-cap site and is homologous to related translational control elements in the 5'-UTR of the light and and heavy ferritin genes. Enhanced translation of APP mRNA provides a mechanism by which IL-1 influences the pathogenesis of AD.  (+info)

Early phenotypic changes in transgenic mice that overexpress different mutants of amyloid precursor protein in brain. (4/2953)

Transgenic mice overexpressing different forms of amyloid precursor protein (APP), i.e. wild type or clinical mutants, displayed an essentially comparable early phenotype in terms of behavior, differential glutamatergic responses, deficits in maintenance of long term potentiation, and premature death. The cognitive impairment, demonstrated in F1 hybrids of the different APP transgenic lines, was significantly different from nontransgenic littermates as early as 3 months of age. Biochemical analysis of secreted and membrane-bound APP, C-terminal "stubs," and Abeta(40) and Abeta(42) peptides in brain indicated that no single intermediate can be responsible for the complex of phenotypic dysfunctions. As expected, the Abeta(42) levels were most prominent in APP/London transgenic mice and correlated directly with the formation of amyloid plaques in older mice of this line. Plaques were associated with immunoreactivity for hyperphosphorylated tau, eventually signaling some form of tau pathology. In conclusion, the different APP transgenic mouse lines studied display cognitive deficits and phenotypic traits early in life that dissociated in time from the formation of amyloid plaques and will be good models for both early and late neuropathological and clinical aspects of Alzheimer's disease.  (+info)

Amyloid precursor protein metabolism in fibroblasts from individuals with one, two or three copies of the amyloid precursor protein (APP) gene. (5/2953)

Protein kinase C (PKC)-activated modulation of amyloid precursor protein (APP) metabolism has been investigated in natural models of altered APP expression due to the presence of one, two or three copies of the APP gene. We show that levels of APP present in human skin fibroblasts strongly influence the effect of PKC activation of soluble APP (sAPP) release. Thus fibroblasts derived from a patient with a deletion in chromosome 21 including the APP locus (Delta21) had lower levels of both APP mRNA and cell-associated APP, and showed an exaggerated phorbol-ester-induced sAPP release, when compared with fibroblasts from control individuals. In contrast, fibroblasts from chromosome 21 trisomic Down's syndrome patients failed to show a concentration-dependent response to phorbol ester treatment. These results suggest that the levels of APP expression can affect the degree of response to PKC-mediated modulation of the metabolism of this protein.  (+info)

Regulation of beta-amyloid secretion by FE65, an amyloid protein precursor-binding protein. (6/2953)

The principal component of Alzheimer's amyloid plaques, Abeta, derives from proteolytic processing of the Alzheimer's amyloid protein precursor (APP). FE65 is a brain-enriched protein that binds to APP. Although several laboratories have characterized the APP-FE65 interaction in vitro, the possible relevance of this interaction to Alzheimer's disease has remained unclear. We demonstrate here that APP and FE65 co-localize in the endoplasmic reticulum/Golgi and possibly in endosomes. Moreover, FE65 increases translocation of APP to the cell surface, as well as both alphaAPPs and Abeta secretion. The dramatic (4-fold) FE65-dependent increase in Abeta secretion suggests that agents which inhibit the interaction of FE65 with APP might reduce Abeta secretion in the brain and therefore be useful for preventing or slowing amyloid plaque formation.  (+info)

Mechanism of the cleavage specificity of Alzheimer's disease gamma-secretase identified by phenylalanine-scanning mutagenesis of the transmembrane domain of the amyloid precursor protein. (7/2953)

Proteolytic processing of the amyloid precursor protein by beta-secretase yields A4CT (C99), which is cleaved further by the as yet unknown gamma-secretase, yielding the beta-amyloid (Abeta) peptide with 40 (Abeta40) or 42 residues (Abeta42). Because the position of gamma-secretase cleavage is crucial for the pathogenesis of Alzheimer's disease, we individually replaced all membrane-domain residues of A4CT outside the Abeta domain with phenylalanine, stably transfected the constructs in COS7 cells, and determined the effect of these mutations on the cleavage specificity of gamma-secretase (Abeta42/Abeta40 ratio). Compared with wild-type A4CT, mutations at Val-44, Ile-47, and Val-50 led to decreased Abeta42/Abeta40 ratios, whereas mutations at Thr-43, Ile-45, Val-46, Leu-49, and Met-51 led to increased Abeta42/Abeta40 ratios. A massive effect was observed for I45F (34-fold increase) making this construct important for the generation of animal models for Alzheimer's disease. Unlike the other mutations, A4CT-V44F was processed mainly to Abeta38, as determined by mass spectrometry. Our data provide a detailed model for the active site of gamma-secretase: gamma-secretase interacts with A4CT by binding to one side of the alpha-helical transmembrane domain of A4CT. Mutations in the transmembrane domain of A4CT interfere with the interaction between gamma-secretase and A4CT and, thus, alter the cleavage specificity of gamma-secretase.  (+info)

Plaque-independent disruption of neural circuits in Alzheimer's disease mouse models. (8/2953)

Autosomal dominant forms of familial Alzheimer's disease (FAD) are associated with increased production of the amyloid beta peptide, Abeta42, which is derived from the amyloid protein precursor (APP). In FAD, as well as in sporadic forms of the illness, Abeta peptides accumulate abnormally in the brain in the form of amyloid plaques. Here, we show that overexpression of FAD(717V-->F)-mutant human APP in neurons of transgenic mice decreases the density of presynaptic terminals and neurons well before these mice develop amyloid plaques. Electrophysiological recordings from the hippocampus revealed prominent deficits in synaptic transmission, which also preceded amyloid deposition by several months. Although in young mice, functional and structural neuronal deficits were of similar magnitude, functional deficits became predominant with advancing age. Increased Abeta production in the context of decreased overall APP expression, achieved by addition of the Swedish FAD mutation to the APP transgene in a second line of mice, further increased synaptic transmission deficits in young APP mice without plaques. These results suggest a neurotoxic effect of Abeta that is independent of plaque formation.  (+info)

Novel neuritic clusters with accumulations of amyloid precursor protein and amyloid precursor-like protein 2 immunoreactivity...
TY - JOUR. T1 - Novel neuritic clusters with accumulations of amyloid precursor protein and amyloid precursor-like protein 2 immunoreactivity in brain regions damaged by thiamine deficiency. AU - Calingasan, Noel Y.. AU - Gandy, Samuel E.. AU - Baker, Harriet. AU - Sheu, Kwan Fu Rex. AU - Smith, Jonathan D.. AU - Lamb, Bruce T.. AU - Gearhart, John D.. AU - Buxbaum, Joseph D.. AU - Harper, Clive. AU - Selkoe, Dennis J.. AU - Price, Donald L.. AU - Sisodia, Sangram S.. AU - Gibson, Gary E.. PY - 1996/9/1. Y1 - 1996/9/1. N2 - Experimental thiamine deficiency (TD) is a classical model of a nutritional deficit associated with a generalized impairment of oxidative metabolism and selective cell loss in the brain. In rats, TD-induced cell degeneration is accompanied by an accumulation of amyloid precursor protein (APP)/amyloid precursor-like protein 2 (APLP2) immunoreactivity in abnormal neurites and perikarya along the periphery of, or scattered within, the lesion. Prompted by these data and our ...
https://indiana.pure.elsevier.com/en/publications/novel-neuritic-clusters-with-accumulations-of-amyloid-precursor-p
Anti-β-Amyloid Precursor-Like Protein 1, C-Terminal (643-653) Rabbit pAb | 171615Anti-β-Amyloid Precursor-Like Protein 1, C-Terminal (643-653) Rabbit pAb | 171615
Anti-β-Amyloid Precursor-Like Protein 1, C-Terminal (643-653) Rabbit pAb - Find MSDS or SDS, a COA, data sheets and more information.
https://www.merckmillipore.com/AE/en/product/Anti-Amyloid-Precursor-Like-Protein-1-C-Terminal-643-653-Rabbit-pAb,EMD_BIO-171615
Purification and aggregation of the amyloid precursor protein intracellular domain<...Purification and aggregation of the amyloid precursor protein intracellular domain<...
TY - JOUR. T1 - Purification and aggregation of the amyloid precursor protein intracellular domain. AU - El Ayadi, Amina. AU - Stieren, Emily S.. AU - Barral, José M.. AU - Oberhauser, Andres F.. AU - Boehning, Darren. PY - 2012/8/28. Y1 - 2012/8/28. N2 - Amyloid precursor protein (APP) is a type I transmembrane protein associated with the pathogenesis of Alzheimers disease (AD). APP is characterized by a large extracellular domain and a short cytosolic domain termed the APP intracellular domain (AICD). During maturation through the secretory pathway, APP can be cleaved by proteases termed α, β, and γ-secretases1. Sequential proteolytic cleavage of APP with β and γ-secretases leads to the production of a small proteolytic peptide, termed Aβ, which is amyloidogenic and the core constituent of senile plaques. The AICD is also liberated from the membrane after secretase processing, and through interactions with Fe65 and Tip60, can translocate to the nucleus to participate in transcription ...
https://researchexperts.utmb.edu/en/publications/purification-and-aggregation-of-the-amyloid-precursor-protein-int
The Rat Central Nervous System Expresses Alzheimers Amyloid Precursor Protein APP<sub>695</sub>, but Not APP<sub>677</sub...
TY - JOUR. T1 - The Rat Central Nervous System Expresses Alzheimers Amyloid Precursor Protein APP695, but Not APP677 (L‐APP Form). AU - Ohgami, Tetsuya. AU - Kitamoto, Tetsuyuki. AU - Tateishi, Jun. PY - 1993/10. Y1 - 1993/10. N2 - Abstract: A novel splicing form of βA4 amyloid precursor protein (APP) lacking exon 15, corresponding to 18 residues, was first reported in leukocytes and then in ubiquitous organs. To determine which APP molecules (APP695, APP751, or APP770) either with (N‐APP) or without (L‐APP; leukocytederived APP) exon 15 were expressed in various organs, we investigated the alternative splicing at exon 15 in the rat brain, kidney, heart, and testis by a PCR analysis of reverse‐transcribed RNA and Southern blot analysis. Regarding APP695 without exons 7 and 8, L‐APP was either seldom or never expressed in the brain, whereas both N‐ and L‐APP were expressed in other organs. On the other hand, regarding APP751/770 containing exon 7, which codes for the Kunitz‐type ...
https://tohoku.pure.elsevier.com/en/publications/the-rat-central-nervous-system-expresses-alzheimers-amyloid-precu
Production of glycosylated soluble amyloid precursor protein alpha (sAPPalpha) in Leishmania tarentolae - MDC RepositoryProduction of glycosylated soluble amyloid precursor protein alpha (sAPPalpha) in Leishmania tarentolae - MDC Repository
Soluble amyloid precursor protein alpha (sAPPalpha) is a cleavage product of the amyloid precursor protein (APP), the etiologic agent in Alzheimers disease (AD). Reduced expression of sAPPalpha was previously found in the brains of AD patients, and it was suggested that sAPPalpha might counteract neurotoxic effects of Abeta, another APP cleavage product with enhanced abundance in Alzheimers diseased brains. However, little is known about the biological functions of sAPPalpha. Thus, efficient production of this protein is a prerequisite for further studies. The unicellular eukaryotic parasite Leishmania tarentolae has recently emerged as a promising expression system for eukaryotic proteins due to its ability to posttranslationally modify proteins combined with easy cultivation and high protein yield. Interestingly, sAPPalpha produced in L. tarentolae was biologically active and glycosylated. In contrast to nonglycosylated sAPPalpha expressed in Eschericha coli, it also featured higher ...
http://edoc.mdc-berlin.de/12944/
Gene expression profiles of transcripts in amyloid precursor protein transgenic mice: Up-regulation of mitochondrial metabolism...Gene expression profiles of transcripts in amyloid precursor protein transgenic mice: Up-regulation of mitochondrial metabolism...
TY - JOUR. T1 - Gene expression profiles of transcripts in amyloid precursor protein transgenic mice. T2 - Up-regulation of mitochondrial metabolism and apoptotic genes is an early cellular change in Alzheimers disease. AU - Reddy, P. Hemachandra. AU - McWeeney, Shannon. AU - Park, Byung S.. AU - Manczak, Maria. AU - Gutala, Ramana V.. AU - Partovi, Dara. AU - Jung, Youngsin. AU - Yau, Vincent. AU - Searles, Robert. AU - Mori, Motomi. AU - Quinn, Joseph. N1 - Funding Information: The authors thank Sandra Oster, Neurological Sciences Institute, Oregon Health and Science University, for critical reading of the manuscript. This research was supported in part by the Alzheimers Association of Oregon, the Medical Research Foundation of Oregon, the American Federation for Aging Research, a pilot grant from the Alzheimers Disease Center of Oregon, P30 AG08017, and AG22643 (to P.H.R.) and Department of Veterans Affairs Advanced Research Career Development Award and NIH-AT0006 (to J.Q.).. PY - ...
https://ohsu.pure.elsevier.com/en/publications/gene-expression-profiles-of-transcripts-in-amyloid-precursor-prot-2
Localization of Genes Potentially Controlling Susceptibility to the Lethal Effects of Alzheimers Amyloid Precursor Protein in...Localization of Genes Potentially Controlling Susceptibility to the Lethal Effects of Alzheimers Amyloid Precursor Protein in...
Variation in the susceptibility to the lethal effects of Alzheimers Amyloid Precursor Protein (APP) transgene exists among various mouse strains. Inbred FVB/N mice, expressing high levels of the transgene-encoded APP, die prior to 200 days, while inbred 129.Tg2576 mice carrying the transgene are far less susceptible. When the two strains are crossed, (FVB/Nxl29.Tg2576) FI mice survive, as does the 129.Tg2576 parent. Intercross and backcross offspring survived at rates of 60% and 35%, respectively, at 200 days signaling the presence of a polygenic trait. The goal of this study was to establish a linkage to genes affecting susceptibility to the APP transgene. The possible quantitative trait loci (QTL) were established using various genetic markers scattered throughout the genome. The presence of multiple QTLs is possible from the data obtained; however, an increased chance of type I errors (false positives) exists due to the large number of markers used for the genome scan ...
https://scholars.carroll.edu/handle/20.500.12647/2974
APBA2 (amyloid beta precursor protein binding family A member 2)APBA2 (amyloid beta precursor protein binding family A member 2)
APBA2 (amyloid beta precursor protein binding family A member 2), Authors: Dessen P. Published in: Atlas Genet Cytogenet Oncol Haematol.
http://atlasgeneticsoncology.org/Genes/GC_APBA2.html
MAPPING THE TRANSCRIPTIONAL REGULATORY NETWORK OF THE AMYLOID PRECURSOR PROTEIN INTRACELLULAR DOMAIN (AICD) | ScholarBank@NUSMAPPING THE TRANSCRIPTIONAL REGULATORY NETWORK OF THE AMYLOID PRECURSOR PROTEIN INTRACELLULAR DOMAIN (AICD) | [email protected]
AICD, the C-terminal tail generated from the proteolytic cleavage of the Amyloid Precursor Protein (APP), has been generating interest for its transcriptional modulatory roles. AICD has been hypothesized to have such a function as it is generated by a gamma-secretase-mediated regulated intramembrane proteolysis step, analogous to the generation of Notch intracellular domain (NICD), a well-known transcriptional regulator, from Notch. The AICD/Fe65/Tip60 ternary complex has been proposed as the working transcriptional regulatory complex and some of its target genes have been reported. However, our knowledge of the functions of AICD is still limited due to difficulties in detecting and manipulating the rapidly degraded peptide. Looking at AICD transcription modulation targets from a genome-wide perspective will aid our understanding of the role of AICD tremendously. To this end, AICD chromatin binding sites were investigated from a genome-wide perspective by performing Chromatin Immunoprecipitation ...
http://scholarbank.nus.edu.sg/handle/10635/37860
The Functions of the Amyloid Precursor Protein Gene and Its Derivative Peptides: I Molecular Biology and Metabolic ProcessingThe Functions of the Amyloid Precursor Protein Gene and Its Derivative Peptides: I Molecular Biology and Metabolic Processing
The amyloid precursor protein gene (APP) and its derivative peptides have important functions in the central nervous system. APP and Aβ fulfil criteria as neuractive peptides: presence, release and identity of action. Aβ is a peptide of 1 - 43 amino acids in length, derived from APP and the major component of the core of neuritic plaques found in Alzheimers disease. Analysis of the cDNA of Aβ revealed its origins from the larger precursor protein. There are at least four types of mRNA generated by alternative splicing of exons 7 and 8. Exon 7 encodes a 57 amino acid sequence found in the extracellular domain with major homology to the Kunitz-type of serine protease inhibitors. APP is cleaved by three secretases known as α, β, and γ secretase which act on APP at different sites producing various fragments of differing amino acid length. The γ secretase is a macromolecular enzyme complex composed of presenilin 1, 2 and other molecular constitutents essential for its function.
https://www.scirp.org/Journal/PaperInformation.aspx?PaperID=5533
Tol2 Gene Trap Integrations in the Zebrafish Amyloid Precursor Protein by Hsin-Kai Liao, Ying Wang et al.Tol2 Gene Trap Integrations in the Zebrafish Amyloid Precursor Protein by Hsin-Kai Liao, Ying Wang et al.
Background-The single spanning transmembrane amyloid precursor protein (APP) and its proteolytic product, amyloid-beta (Aβ) peptide, have been intensely studied due to their role in the pathogenesis of Alzheimers disease. However, the biological role of the secreted ectodomain of APP, which is also generated by proteolytic cleavage, is less well understood. Here, we report Tol2 red fluorescent protein (RFP) transposon gene trap integrations in the zebrafish amyloid precursor protein a (appa) and amyloid precursor-like protein 2 (aplp2) genes. The transposon integrations are predicted to disrupt the appa and aplp2 genes to primarily produce secreted ectodomains of the corresponding proteins that are fused to RFP. Results-Our results indicate the Appa-RFP and Aplp2 fusion proteins are likely secreted from the central nervous system and accumulate in the embryonic veins independent of blood flow. Conclusions-The zebrafish appa and aplp2 transposon insertion alleles will be useful for investigating the
https://lib.dr.iastate.edu/gdcb_las_pubs/49/
Cell Cycle-Dependent Regulation of the Phosphorylation and Metabolism of the Alzheimer Amyloid Precursor Protein - CSHL...Cell Cycle-Dependent Regulation of the Phosphorylation and Metabolism of the Alzheimer Amyloid Precursor Protein - CSHL...
Accumulation of the amyloid A beta peptide, which is derived from a larger precursor protein (APP), and the formation of plaques, are major events believed to be involved in the etiology of Alzheimers disease. Abnormal regulation of the metabolism of APP may contribute to the deposition of plaques. APP is an integral membrane protein containing several putative phosphorylation sites within its cytoplasmic domain. We report here that APP is phosphorylated at Thr668 by p34(cdc2) protein kinase (cdc2 kinase) in vitro, and in a cell cycle-dependent manner in vivo. At the G(2)/M phase of the cell cycle, when APP phosphorylation is maximal, the levels of mature APP (mAPP) and immature APP (imAPP) do not change significantly. However, imAPP is altered qualitatively. Furthermore, the level of the secreted extracellular N-terminal domain (APP(S)) is decreased and that of the truncated intracellular C-terminal fragment (APP(COOH)) is increased. These findings suggest the possibility that ...
https://repository.cshl.edu/id/eprint/31460/
Three-Dimensional Structure Of The Amyloid Precursor Protein Intracellular Domain (AICD) In Complex With Human FE65-PTB2 -...Three-Dimensional Structure Of The Amyloid Precursor Protein Intracellular Domain (AICD) In Complex With Human FE65-PTB2 -...
9150PRTHomo sapiens 1Val Met Leu Lys Lys Lys Gln Tyr Thr Ser Ile His His Gly Val Val1 5 10 15Glu Val Asp Ala Ala Val Thr Pro Glu Glu Arg His Leu Ser Lys Met 20 25 30Gln Gln Asn Gly Tyr Glu Asn Pro Thr Tyr Lys Phe Phe Glu Gln Met 35 40 45Gln Asn 502134PRTHomo sapiens 2Ala Pro Lys Asn Glu Leu Val Gln Lys Phe Gln Val Tyr Tyr Leu Gly1 5 10 15Asn Val Pro Val Ala Lys Pro Val Gly Val Asp Val Ile Asn Gly Ala 20 25 30Leu Glu Ser Val Leu Ser Ser Ser Ser Arg Glu Gln Trp Thr Pro Ser 35 40 45His Val Ser Val Ala Pro Ala Thr Leu Thr Ile Leu His Gln Gln Thr 50 55 60Glu Ala Val Leu Gly Glu Cys Arg Val Arg Phe Leu Ser Phe Leu Ala65 70 75 80Val Gly Arg Asp Val His Thr Phe Ala Phe Ile Met Ala Ala Gly Pro 85 90 95Ala Ser Phe Cys Cys His Met Phe Trp Cys Glu Pro Asn Ala Ala Ser 100 105 110Leu Ser Glu Ala Val Gln Ala Ala Cys Met Leu Arg Tyr Gln Lys Cys 115 120 125Leu Asp Ala Arg Ser Gln 130325DNAArtificialPrimer APP_C50_F 3gtaccatatg gtgatgctga agaag 25432DNAArtificialPrimer APP_C50_R 4gtacaagctt ctagttctgc atctgctcaa ...
http://www.patentsencyclopedia.com/app/20110118439
Transgenic Mice Overexpressing Amyloid Precursor Protein Exhibit Early Metabolic Deficits and a Pathologically Low Leptin State...Transgenic Mice Overexpressing Amyloid Precursor Protein Exhibit Early Metabolic Deficits and a Pathologically Low Leptin State...
Weight loss is a prominent early feature of Alzheimers disease (AD) that often precedes the cognitive decline and clinical diagnosis. While the exact pathogenesis of AD remains unclear, accumulation of amyloid-β (Aβ) derived from the amyloid precursor protein (APP) in the brain is thought to lead to the neuronal dysfunction and death underlying the dementia. In this study, we examined whether transgenic mice overexpressing the Swedish mutation of APP (Tg2576), recapitulating selected features of AD, have hypothalamic leptin signaling dysfunction leading to early body weight deficits. We found that 3-month-old Tg2576 mice, before amyloid plaque formation, exhibit decreased weight with markedly decreased adiposity, low plasma leptin levels, and increased energy expenditure without alterations in feeding behavior. The expression of the orexigenic neuropeptide Y (NPY) in the hypothalamus to the low leptin state was abnormal at basal and fasting conditions. In addition, arcuate NPY neurons ...
https://www.jneurosci.org/content/34/27/9096.short
Alvocidib biological activity | Role of NK1 and NK2 receptors in mouse gastric mechanical activityAlvocidib biological activity | Role of NK1 and NK2 receptors in mouse gastric mechanical activity
Processing from the amyloid proteins precursor (APP) from the and secretases potential clients to the creation of two little peptides, amyloid as well as the APP intracellular site (Help, or called elsewhere AICD). in conjunction with Fe65 by 1st displaying that although Fe65 enters the nucleus in the lack of full-length APP, JIP-1 will not. Additionally, JIP-1-induced activation can be Suggestion60 3rd party, whereas a complicated with Help, Fe65, and Suggestion60 can be shaped for Fe65-induced activation. Finally, and most interestingly probably, we display that even though the APP family APLP1 and APLP2 (for amyloid precursor-like protein) can cause activation in combination Rabbit polyclonal to AACS with Fe65, APLP1 and APLP2 show little or no activation in combination with JIP-1. This activity for the AID fragment may help explain the unique functions of APP relative to its other family members, and changes in gene expression found in Alzheimers disease. The importance of amyloid protein ...
https://stopvivisection.info/tag/alvocidib-biological-activity/
The apolipoprotein E epsilon 4 allele does not influence the clinical expression of the amyloid precursor protein gene codon...
In 31 symptomatic and 5 asymptomatic carriers of the amyloid precursor protein (APP) gene codon 693 mutation, 10 family members without mutation, and 5 carriers of the APP gene codon 692 mutation (3 with early-onset Alzheimer dementia, 2 with cerebral hemorrhage), a high frequency of the apolipoprotein E epsilon 4 allele was found. Age at onset, age at death, occurrence of dementia, and number of strokes did not differ between APP gene mutation carriers with or without epsilon 4 allele, showing that the clinical expression of these APP mutations is not influenced by the apolipoprotein E gene.
https://www.ndph.ox.ac.uk/publications/937775
Amyloid Precursor Protein
Growth factors are substances that are capable of stimulating cellular proliferation, differentiation, as well as growth. Another probable hypothesis is that the membrane-bound APP may be involved in cell signaling, which is the complex communication system used by cells to govern basic cellular activities and actions. Molecules of APP that are not cleaved by α-secretase are capable of forming internalized endocytic compartments, which in turn are subsequently cleaved by β- and γ- secretases (6). γ- secretase carries out proteolytic modification further by processing the membrane-bound peptide into the amyloid beta (Aβ) peptide form (7). Generation of the Aβ peptide is borne solely from the cleavage of APP in which the amyloid precursor protein intracellular domain (AICD) is released and deposited in aggregated fibrils in senile plaques. Other APP protein family members do not form the Aβ peptide deposits on cleavage (6). It is important to restate that the physiological function of ...
https://chemistry.berea.edu/~biochemistry/2009/Adam/
Dynamics of β-Amyloid Reductions in Brain, Cerebrospinal Fluid, and Plasma of β-Amyloid Precursor Protein Transgenic Mice...Dynamics of β-Amyloid Reductions in Brain, Cerebrospinal Fluid, and Plasma of β-Amyloid Precursor Protein Transgenic Mice...
Handling of Mice. The Tg2576 mice were developed by Karen Hsaio (Hsiao et al., 1996) and licensed from the Mayo Foundation for Medical Education and Research (Rochester, MN). Male Tg2576 transgenic mice were bred to normal C57BL6/SJL females at the Bristol-Myers Squibb facility in Wallingford, CT. Mice were housed with a 6:00 AM to 6:00 PM light/dark cycle and allowed free access to food and water. Both male and female mice were used in these studies, and although no differences in Aβ were observed between them, only one sex was used in a single study. Young Tg2576 mice were used between 3 and 6 months of age, whereas aged animals were used at 14 to 17 months. BMS-299897 was synthesized by the Medicinal Chemistry groups of SIBIA Neurosciences, Inc. (now Merck Research Laboratories, San Diego, CA) and Bristol-Myers Squibb. Animals were dosed by oral gavage in a volume of 6 ml/kg in polyethylene glycol, average molecular weight of 400, or a vehicle consisting of 10% propylene glycol, 7.5% ...
http://jpet.aspetjournals.org/content/312/2/635.long
β-Secretase Cleavage of Alzheimers Amyloid Precursor Protein by the Transmembrane Aspartic Protease BACE | Scienceβ-Secretase Cleavage of Alzheimers Amyloid Precursor Protein by the Transmembrane Aspartic Protease BACE | Science
To address the substrate requirements of BACE-IgG, we designed three peptide substrates, each containing 30 amino acids, extending from P21 to P9 to span the β-secretase cleavage site. These peptides represent: (i) APPwt; (ii) APPsw; and (iii) the MV substitution (P1 changed from Met → Val). In intact cells, endogenous β-secretase cleaves APPsw much better than APPwt, but the MV mutant is not cleaved (22). Pure BACE-IgG cleaves the pure wt peptide with a specific activity of approximately 9 nmol/min/mg, demonstrating that BACE acts as a protease (Fig. 8B). We detect only one cleavage and this is at the correct Asp1 site (24). As expected for β-secretase, the specific activity of BACE-IgG for the Swedish substrate is much higher than for the wt substrate, whereas cleavage of the MV mutant is not detectable at all (Fig. 8B).. Experiments with intact cells suggest that β-secretase has an acidic pH optimum (14, 15). Indeed, a pH titration of BACE activity shows an optimum at pH 4.5 for both ...
https://science.sciencemag.org/content/286/5440/735?ijkey=a076c7e49be3e4dc4184d0099ee950f3562974f3&keytype2=tf_ipsecsha
Pathological α-synuclein transmission initiated by binding lymphocyte-activation gene 3 | SciencePathological α-synuclein transmission initiated by binding lymphocyte-activation gene 3 | Science
The selectivity of LAG3, neurexin 1β, and APLP1 and related transmembrane proteins for α-syn-biotin PFF versus α-syn-biotin monomers was determined via the ratio of Kd values (Fig. 1B). LAG3 exhibited the highest selectivity with a ratio of 38, followed by neurexin 1β with a ratio of 11 and APLP1 with a ratio of 7. The binding of α-syn-biotin PFF to LAG3 was specific because α-syn-biotin PFF does not bind to the CD4 receptor, which has 20% homology to LAG3 (Fig. 1B and fig. S4). In addition to α-syn-biotin PFF binding to neurexin 1β, it also binds to neurexin 3β and mildly binds to neurexin 1α and neurexin 2β (Fig. 1B). α-Syn-biotin PFF does not bind the amyloid precursor protein (APP) or the amyloid precursor-like protein 2 (APLP2), suggesting that the binding to APLP1 was specific (Fig. 1B). Because LAG3 exhibited the highest selectivity for α-syn-biotin PFF, it was advanced for further study. No LAG3 immunoreactive band was observed in HEK293FT and SH-SY5Y cells, which is ...
https://science.sciencemag.org/content/353/6307/aah3374?ijkey=3fbafef0d14e262734312ec90f9c3a4ec766beba&keytype2=tf_ipsecsha
Presenilin 1 mutations increase amyloid precursor protein production and proteolysis in Xenopus laevis oocytes<...
TY - JOUR. T1 - Presenilin 1 mutations increase amyloid precursor protein production and proteolysis in Xenopus laevis oocytes. AU - Heyn, Sietske N.. AU - Vulliet, Philip R. PY - 2001/6/22. Y1 - 2001/6/22. N2 - Recent findings suggest that Presenilin 1 (PS1) mutations play a major role in the development of Alzheimers disease (AD) by increasing the production of the beta amyloid peptide (Aβ). The exact mechanism whereby mutations in PS1 lead to this effect is not clear. To examine the question of how PS1 might be involved in amyloid precursor protein (APP) processing, we constructed a chimera of human APP695 fused at the C-terminal to enhanced green fluorescent protein (EGFP). This construct was injected into Xenopus laevis oocytes in the presence of wild type PS1 or one of three PS1 mutations associated with AD. The cellular location of the APP695-EGFP construct was examined by fluorescent confocal microscopy. In addition, membrane fractions of oocytes expressing APP695-EGFP in the presence ...
https://ucdavis.pure.elsevier.com/en/publications/presenilin-1-mutations-increase-amyloid-precursor-protein-product
Amyloid Precursor Protein (APP) controls excitatory/inhibitory synaptic inputs by regulating the transcriptional activator...
Sequential proteolysis of the amyloid precursor protein (APP) and amyloid-beta petide (Abeta) release is an upstream event in Alzheimers disease (AD) pathogenesis. The function of APP in neuronal physiology is still, however, poorly understood. Along with its paralog APP-like Proteins 1 and 2 (APLP1-2), APP is involved in neurite formation and synaptic function by mechanisms that are not elucidated. APP is a single-pass transmembrane protein expressed at high levels in the brain that resembles a cell adhesion molecule or a membrane receptor, suggesting that its function relies on cell interaction processes and/or activation of intracellular pathways of signal transduction. Along this line, the APP intracellular domain (AICD) was reported to act as a transcriptional factor for targeted gene activation that mediates physiological APP functions. Here, we used an unbiased transcriptome-based approach to identify the genes transcriptionally regulated by APP in the rodent embryonic cortex and upon ...
https://www.meta.org/papers/amyloid-precursor-protein-app-controls/990504340
feh-1 and apl-1, the Caenorhabditis elegans orthologues of mammalian Fe65 and β-amyloid precursor protein genes, are involved...feh-1 and apl-1, the Caenorhabditis elegans orthologues of mammalian Fe65 and β-amyloid precursor protein genes, are involved...
In mammals, many of the proteins taking part in the complex network of interactions centred at the cytosolic domain of APP belong to gene families. This is in fact the case for APP-like genes, as well as for Fe65- and X11-like members. APP-like gene family members have been analysed in depth, in mammals, by reverse genetics. However, their redundancy prevented the generation of clear phenotypes from murine knock-outs of the single APP, APLP1 or APLP2 genes ( Zheng et al., 1995; von Koch et al., 1997; Heber et al., 2000), whereas mice with combined knock-outs displayed severe phenotypes, dying early and post-natally. Taken together, the functions of these genes have been proposed as essential and partially redundant in mammals ( Heber et al., 2000). A similar phenotype, although not strictly predictable, might occur if reverse genetic approaches were used with the mammalian Fe65 gene family members. This was one of the reasons that prompted us to investigate potential Fe65-like genes in the ...
http://jcs.biologists.org/content/115/7/1411
Recombinant Human Amyloid Precursor Protein (ab124588)Recombinant Human Amyloid Precursor Protein (ab124588)
Recombinant Human Amyloid Precursor Protein Protein fragment datasheet (ab124588). Abcam offers quality products including antibodies, assays and other…
http://www.abcam.co.jp/recombinant-human-amyloid-precursor-protein-ab124588.html
ALZFORUM | NETWORKING FOR A CUREALZFORUM | NETWORKING FOR A CURE
Iijima K, Ando K, Takeda S, Satoh Y, Seki T, Itohara S, Greengard P, Kirino Y, Nairn AC, Suzuki T. Neuron-specific phosphorylation of Alzheimers beta-amyloid precursor protein by cyclin-dependent kinase 5 ...
http://www.alzforum.org/papers/neuron-specific-phosphorylation-alzheimers-beta-amyloid-precursor-protein-cyclin-dependent
The role of ADAM10 and ADAM17 in the ectodomain shedding of angiotensin converting enzyme and the amyloid precursor protein. -...The role of ADAM10 and ADAM17 in the ectodomain shedding of angiotensin converting enzyme and the amyloid precursor protein. -...
Numerous transmembrane proteins, including the blood pressure regulating angiotensin converting enzyme (ACE) and the Alzheimers disease amyloid precursor protein (APP), are proteolytically shed from the plasma membrane by metalloproteases. We have used an antisense oligonucleotide (ASO) approach to delineate the role of ADAM10 and tumour necrosis factor-α converting enzyme (TACE; ADAM17) in the ectodomain shedding of ACE and APP from human SH-SY5Y cells. Although the ADAM10 ASO and TACE ASO significantly reduced (, 81%) their respective mRNA levels and reduced the α-secretase shedding of APP by 60% and 30%, respectively, neither ASO reduced the shedding of ACE. The mercurial compound 4-aminophenylmercuric acetate (APMA) stimulated the shedding of ACE but not of APP. The APMA-stimulated secretase cleaved ACE at the same Arg-Ser bond in the juxtamembrane stalk as the constitutive secretase but was more sensitive to inhibition by a hydroxamate-based compound. The APMA-activated shedding of ACE ...
http://eprints.lancs.ac.uk/9449/
A novel γ-secretase assay based on detection of the putative C-terminal fragment-γ of amyloid β protein precursor<...
TY - JOUR. T1 - A novel γ-secretase assay based on detection of the putative C-terminal fragment-γ of amyloid β protein precursor. AU - Pinnix, Inga. AU - Musunuru, Usha. AU - Tun, Han W. AU - Sridharan, Arati. AU - Golde, Todd. AU - Eckman, Christopher. AU - Ziani-Cherif, Chewki. AU - Onstead, Luisa. AU - Sambamurti, Kumar. PY - 2001/1/5. Y1 - 2001/1/5. N2 - Alzheimers disease is characterized by the deposits of the 4-kDa amyloid β peptide (Aβ). The Aβ protein precursor (APP) is cleaved by β-secretase to generate a C-terminal fragment, CTFβ, which in turn is cleaved by γ-secretase to generate Aβ. Alternative cleavage of the APP by α-secretase at Aβ16/17 generates the C-terminal fragment, CTFα. In addition to Aβ, endoproteolytic cleavage of CTFα and CTFβ by γ-secretase should yield a C-terminal fragment of 57-59 residues (CTFγ). However, CTFγ has not yet been reported in either brain or cell lysates, presumably due to its instability in vivo. We detected the in vitro ...
https://mayoclinic.pure.elsevier.com/en/publications/a-novel-%CE%B3-secretase-assay-based-on-detection-of-the-putative-c-te
Neuronal overexpression of mutant amyloid precursor protein results in prominent deposition of cerebrovascular amyloid | PNASNeuronal overexpression of mutant amyloid precursor protein results in prominent deposition of cerebrovascular amyloid | PNAS
As has been described in naturally occurring CAA (1, 5), vascular amyloid deposition in APP23 mice is most frequently found in arteries/arterioles and occurs most often in vessels outside the brain parenchyma proper (e.g., pia, fissures). The arterial predilection suggests that an anatomical difference between arteries and veins (e.g., presence of significant amounts of smooth muscle) could contribute to the development of CAA. Indeed, it has been hypothesized that Aβ is deposited by vascular smooth muscle cells and/or perivascular microglia, and APP expression and Aβ production by vascular cells have been well documented (22, 23). These reports and the observation that vessels apart from the neuropil are more often affected strongly implicate local production or circulating Aβ as an important source, although these hypotheses fail to explain the exclusive localization of CAA to cerebral vessels. In the present study, through examination of APP transgenic mice on an App-null background, we ...
https://www.pnas.org/content/96/24/14088?ijkey=ba11ec8947e2071943af1d876e2f0c9387847ffe&keytype2=tf_ipsecsha
Human Amyloid Precursor Protein (APP) ELISA Kit - emlinhibitor-emlinhibitor.comHuman Amyloid Precursor Protein (APP) ELISA Kit - emlinhibitor-emlinhibitor.com
Synonyms: Amyloid Beta A4 Protein, APPI, ABPP, Alzheimer Disease Amyloid Protein, Beta-amyloid Precursor Protein, Cerebral Vascular Amyloid Peptide, CVAP, PreA4, Protease Nexin-II, PN-II ...
https://www.emlinhibitor.com/2017/06/29/Human-Amyloid-Precursor-Protein-APP-ELISA-Kit/
Aging | Effects of senescence and angiotensin II on expression and processing of amyloid precursor protein in human cerebral...
The present study was designed to determine the effects of senescence and angiotensin II (Ang II) on expression and processing of amyloid precursor protein (APP) in human brain microvascular endothelial cells (BMECs). Senescence caused a decrease in APP expression thereby resulting in reduced secretion of soluble APPα (sAPPα). In contrast, β-site APP cleaving enzyme (BACE1) expression and production of amyloid β (Aβ)40 were increased in senescent endothelium. Importantly, in senescent human BMECs, treatment with BACE1 inhibitor IV inhibited Aβ generation and increased sAPPα production by enhancing a disintegrin and metalloprotease (ADAM)10 expression. Furthermore, Ang II impaired expression of ADAM10 and significantly reduced generation of sAPPα in senescent human BMECs. This inhibitory effect of Ang II was prevented by treatment with BACE1 inhibitor IV. Our results suggest that impairment of α-processing and shift to amyloidogenic pathway of APP contribute to endothelial dysfunction induced by
https://www.aging-us.com/figure/101362/f1
APP (Amyloid Precursor Protein), eFluor 570, clone: 22C11, eBioscience™ 100μg; eFluor 570 APP (Amyloid Precursor Protein),...APP (Amyloid Precursor Protein), eFluor 570, clone: 22C11, eBioscience™ 100μg; eFluor 570 APP (Amyloid Precursor Protein),...
APP (Amyloid Precursor Protein), eFluor 570, clone: 22C11, eBioscience™ 100μg; eFluor 570 APP (Amyloid Precursor Protein), eFluor 570, clone: 22C11,...
https://www.fishersci.co.uk/shop/products/app-amyloid-precursor-protein-mouse-efluor-570-clone-22c11-ebioscience-2/15558956
Cystatin Cs Naughty Side-Slowing Aβ Degradation by Cathepsin B | ALZFORUMCystatin Cs Naughty Side-Slowing Aβ Degradation by Cathepsin B | ALZFORUM
As with industrious employees, it is hard to spur greater productivity in an enzyme by simply cracking the whip. However, clearing distractions might do the trick. Taking this strategy into an Alzheimer disease mouse model, scientists have boosted the activity of an Aβ-degrading enzyme by reducing levels of an endogenous inhibitor. The enzyme, cathepsin B (CatB), caught the attention of Li Gan at the Gladstone Institute of Neurological Disease in San Francisco several years ago when it appeared to prevent buildup of amyloid plaques in the brains of AD mice overexpressing mutant human amyloid precursor protein (APP). In the October 23 Neuron, Gan and colleagues now report that APP mice lacking cystatin C (CysC)-an inhibitor of cysteine proteases including CatB-have lower soluble Aβ levels and reduced Aβ-associated deficits in cognition, behavior, and synaptic plasticity compared to APP/CysC+/+ mice. By crossing the animals onto a CatB-null background, they show that these benefits depend on ...
https://www.alzforum.org/news/research-news/cystatin-cs-naughty-side-slowing-av-degradation-cathepsin-b
Novel mutations introduced at the β-site of amyloid β protein precursor enhance the production of amyloid β peptide by BACE1 in...Novel mutations introduced at the β-site of amyloid β protein precursor enhance the production of amyloid β peptide by BACE1 in...
Abnormal production and accumulation of amyloid-β peptide (Aβ) plays a major role in the pathogenesis of Alzheimers disease (AD). β-secretase (BACE1) is responsible for the cleavage at the β-site in amyloid β protein precursor (AβPP/APP) to generate
https://content.iospress.com/articles/journal-of-alzheimers-disease/jad00409
Increased processing of APLP2 and APP with concomitantformation of APP intracellular domains in BDNF and retinoic acid...Increased processing of APLP2 and APP with concomitantformation of APP intracellular domains in BDNF and retinoic acid...
Increased amyloid-β (Aβ) load in the brain, neurite degeneration, neuronal loss, and decreased levels of several neurotrophins are among the characteristics of Alzheimers disease (AD). Generation of Aβ occurs when the amyloid precursor protein (APP) is proteolytically processed by β- and γ-secretases in the amyloidogenic pathway. However, Aβ formation is prevented if APP is cleaved by α- and γ- secretases in the non-amyloidogenic pathway. The normal function of APP is still not fully known. It seems clear that the different fragments that are produced during proteolytic processing have different bioactive properties. APP and its metabolites have been implicated in neurite outgrowth, synaptogenesis, cell adhesion, neuroprotection and apoptosis.. The aim of this thesis was to investigate how neurotrophic factors affect the synthesis and processing of APP and its two mammalian paralogues the APP-like protein-1 and-2 (APLP1 and APLP2). We also wanted to determine how the expression levels ...
http://su.diva-portal.org/smash/record.jsf?faces-redirect=true&language=no&searchType=SIMPLE&query=&af=%5B%5D&aq=%5B%5B%5D%5D&aq2=%5B%5B%5D%5D&aqe=%5B%5D&pid=diva2%3A280999&noOfRows=50&sortOrder=author_sort_asc&sortOrder2=title_sort_asc&onlyFullText=false&sf=all
Ubiquilin-1 regulates amyloid precursor protein maturation and degradation by stimulating K63-linked polyubiquitination of...Ubiquilin-1 regulates amyloid precursor protein maturation and degradation by stimulating K63-linked polyubiquitination of...
TY - JOUR. T1 - Ubiquilin-1 regulates amyloid precursor protein maturation and degradation by stimulating K63-linked polyubiquitination of lysine 688. AU - Ayadi, Amina El. AU - Stieren, Emily S.. AU - Barral, José M.. AU - Boehning, Darren. PY - 2012/8/14. Y1 - 2012/8/14. N2 - The pathogenesis of Alzheimers disease (AD) is associated with proteolytic processing of the amyloid precursor protein (APP) to an amyloidogenic peptide termed Aβ. Although mutations in APP and the secretase enzymes that mediate its processing are known to result in familial forms of AD, the mechanisms underlying the more common sporadic forms of the disease are still unclear. Evidence suggests that the susceptibility of APP to amyloidogenic processing is related to its intracellular localization, and that secretase-independent degradation may prevent the formation of cytotoxic peptide fragments. Recently, single nucleotide polymorphisms in the UBQLN1 gene have been linked to late-onset AD, and its protein product, ...
https://researchexperts.utmb.edu/en/publications/ubiquilin-1-regulates-amyloid-precursor-protein-maturation-and-de
Amyloid beta antibody | acris-antibodies.com
Amyloid beta precursor protein gene (ABPP) encodes a cell surface receptor and transmembrane precursor protein that is cleaved by secretases to form a…
https://www.acris-antibodies.com/target/amyloid-beta-antibody.htm
Galectin 3- binding protein suppresses amyloid-β production by modulating β-cleavage of amyloid precursor protein<...Galectin 3- binding protein suppresses amyloid-β production by modulating β-cleavage of amyloid precursor protein<...
TY - JOUR. T1 - Galectin 3- binding protein suppresses amyloid-β production by modulating β-cleavage of amyloid precursor protein. AU - Seki, Tsuneyoshi. AU - Kanagawa, Motoi. AU - Kobayashi, Kazuhiro. AU - Kowa, Hisatomo. AU - Yahata, Naoki. AU - Maruyama, Kei. AU - Iwata, Nobuhisa. AU - Inoue, Haruhisa. AU - Toda, Tatsushi. N1 - Funding Information: This work was supported by Japan Society for the Promotion of Science (JSPS) Grant 17H06421 (to M. K.) and by CREST (to H. I., N. I., and T. T.). The authors declare that they have no conflicts of interest with the contents of this article. Publisher Copyright: © 2020 Seki et al. Published by The American Society for Biochemistry and Molecular Biology, Inc.. PY - 2020/3/13. Y1 - 2020/3/13. N2 - Alzheimers disease (AD) is the most common type of dementia, and its pathogenesis is associated with accumulation of β-amyloid (Aβ) peptides. Aβ is produced from amyloid precursor protein (APP) that is sequentially cleaved by β- and γ-secretases. ...
https://pure.fujita-hu.ac.jp/ja/publications/galectin-3-binding-protein-suppresses-amyloid-%CE%B2-production-by-mod
Amyloid precursor protein mRNA levels in Alzheimers disease brainAmyloid precursor protein mRNA levels in Alzheimers disease brain
Insoluble beta-amyloid deposits in Alzheimers disease (AD) brain are proteolytically derived from the membrane bound amyloid precursor protein (APP). The APP gene is differentially spliced to produce isoforms that can be classified into those containing a Kunitz-type serine protease inhibitor domain (K(+), APP(751), APP(770), APRP(365) and APRP(563)), and those without (K(-), APP(695) and APP(714)). Given the hypothesis that Abeta is a result of aberrant catabolism of APP, differential expression of mRNA isoforms containing protease inhibitors might play an active role in the pathology of AD. We took 513 cerebral cortex samples from 90 AD and 81 control brains and quantified the mRNA isoforms of APP with TaqMan real-time RT-PCR. After adjustment for age at death, brain pH and gender we found a change in the ratio of KPI(+) to KPI(-) mRNA isoforms of APP. Three separate probes, designed to recognise only KPI(+) mRNA species, gave increases of between 28% and 50% in AD brains relative to controls ...
http://uu.diva-portal.org/smash/record.jsf?pid=diva2:100376
Antimicrobial activity of peptides derived from human ss-amyloid precursor proteinAntimicrobial activity of peptides derived from human ss-amyloid precursor protein
Antimicrobial peptides are important effector molecules of the innate immune system. Here, we describe that peptides derived from the heparin-binding disulfide-constrained loop region of human beta-amyloid precursor protein are antimicrobial. The peptides investigated were linear and cyclic forms of NWCKRGRKQCKTHPH (NWC15) as well as the cyclic form comprising the C-terminal hydrophobic amino acid extension FVIPY (NWCKRGRKQCKTHPHFVIPY; NWC20c). Compared with the benchmark antimicrobial peptide LL-37, these peptides efficiently killed the Gram-negative bacteria Escherichia coli and Pseudomonas aeruginosa, the Gram-positive Staphylococcus aureus and Bacillus subtilis, and the fungi Candida albicans and Candida parapsilosis. Correspondingly, fluorescence and electron microscopy demonstrated that the peptides caused defects in bacterial membranes. Analogously, the peptides permeabilised negatively charged liposomes. Despite their bactericidal effect, the peptides displayed very limited hemolytic ...
http://uu.diva-portal.org/smash/record.jsf?pid=diva2:510960
The Importance of Cannabis For Alzheimers Patients | ThemocracyThe Importance of Cannabis For Alzheimers Patients | Themocracy
In a 2014 scientific study, researchers have discovered strong evidence of the therapeutic effects of THC found in cannabis, in regards to reversing the brain damage associated with Alzheimers Disease. The results clearly are in favor of low-dose, monitored use of cannabis to lower the levels of amyloid-beta precursor proteins, characteristic of this health problem.. Amyloid-beta precursor proteins are large membrane proteins that support neural health, growth, and repair. Due to the natural aging process and the presence of inflammation, a corrupted version of these proteins may begin to produce, destroying neurons and consequently, the memories, thinking process, and even the personality of the Alzheimers patient.. If THC successfully lowers the level of the corrupted amyloid-beta precursor proteins, does this mean that Alzheimers Disease can be completely reversed? Scientists do not yet have clear-cut and straightforward answers to this important question. Even though the political and ...
http://themocracy.com/the-importance-of-cannabis-for-alzheimers-patients/
Niina Koistinen, licentiatseminarium - Institutionen för neurokemiNiina Koistinen, licentiatseminarium - Institutionen för neurokemi
The amyloid precursor protein (APP) protein has been in the limelight of research on Alzheimer´s disease (AD) pathogenesis because its proteolytic processing gives rise to the neurotoxic amyloid β (Aβ) peptide, the main constituent of amyloid plaques in the brains of AD patients. APP is sequentially processed by at least three different proteases termed α-, β-, and γ-secretases. The proteolytic processing of APP can be divided into two different pathways, the non-amyloidogenic and the amyloidogenic. Whether APP is processed by the non-amyloidogenic or the amyloidogenic pathway is highly dependent on co-localization of APP with the different processing enzymes. Hence, understanding the mechanism underlying regulation of APP trafficking and its related secretases is of great importance in our understanding of AD and AD pathogenesis. The aim of this thesis was to study the processing and trafficking of APP, how it may be regulated by the interaction with the adaptor protein, Fe65, and by a ...
http://www.neurochem.su.se/om-oss/evenemang/niina-koistinen-licentiatseminarium-1.167859
CV. Nuestros investigadores. Investigación. Universidad de NavarraCV. Nuestros investigadores. Investigación. Universidad de Navarra
The Tg2576 mouse, which carries the Swedish mutant form of human beta-amyloid precursor protein (hAPP(swe)), develops Alzheimers Disease (AD)-like phenotype (synaptic pathology, cognitive impairment and beta amyloid -A beta-plaques.) in the absence of significant neuronal loss. We have analyzed the hippocampal proteome of Tg2576, focusing on changes at 7 months of age, when A beta levels begin to increase but cognitive symptoms are still not evident, and at 16 months, when most AD-like features are manifested. Proteins differentially expressed with respect to wild-type animals were grouped according to their biological function and assessed in the context of AD. Metabolic enzymes, propionyl-CoA carboxylase, which has not been previously related to AD, and glutamine synthetase, which is a key enzyme for ammonium removal, were among deregulated proteins. Mitochondria of young animals have to cope with the metabolic stress and elevated ATP demand caused by overexpression of hAPP(swe). ...
https://www.unav.edu/web/investigacion/nuestros-investigadores/detalle-investigadores-cv?investigadorId=28581
Lack of Neurodegeneration in Transgenic Mice Overexpressing Mutant Amyloid Precursor Protein Is Associated with Increased...Lack of Neurodegeneration in Transgenic Mice Overexpressing Mutant Amyloid Precursor Protein Is Associated with Increased...
We have shown that the expression of a number of protective genes and a protective pathway culminating in Bad phosphorylation are increased in mice that overexpress APPSw and have no neuronal loss. Increased levels of IGF-2 mRNA and protein correspond to increased activation of the IGF-1 receptor, activation of Akt and Erk1/2, and phosphorylation of Bad in APPSw mice. The increased expression of TTR and IGF-2 as well as increased phospho-Bad staining in hippocampal neurons was consistent in both preplaque (6 months) and postplaque (12 months) Tg2576 mice. Other conditions, such as the presence of a human tau gene, may be necessary for complete AD pathology. However, taken together, these data imply that the lack of neurodegeneration in APPSw mice is a result of the activation of known cell survival pathways associated with the overexpression of APPSw.. Transthyretin has been shown to bind Aβ and inhibit Aβ aggregation (Schwarzman et al., 1994). In human AD patients the concentration of TTR is ...
http://www.jneurosci.org/content/22/17/7380.long
First person - Eleftheria Pervolaraki | Disease Models & MechanismsFirst person - Eleftheria Pervolaraki | Disease Models & Mechanisms
What are the main advantages and drawbacks of the model system you have used as it relates to the disease you are investigating?. The problems with first-generation Aβ precursor protein (APP) transgenic mice have been well established. In short, many AD mouse models achieve elevated Aβ by overexpressing APP, and then relying upon familial AD mutations to overexpress Aβ. In AD, APP expression is similar between AD and control subjects, with mutations only elevating Aβ40 and Aβ42. The effects of APP overexpression have been studied in mice, and the phenotype is strikingly similar to what one would expect to find as a result of AD pathology, both in terms of behaviour and molecular biology of excitatory synapses. Hence, dissociating the effect of Aβ from APP overexpression has been challenging, especially when many researchers use wild-type and not APP-overexpressing mice as controls.. The new generation of mice called AppNL-G-F created by Saito and colleagues (co-authors) express APP at ...
https://dmm.biologists.org/content/12/9/dmm042408
Imaging distinct conformational states of amyloid-β fibrils in Alzheimers disease using novel luminescent probesImaging distinct conformational states of amyloid-β fibrils in Alzheimers disease using novel luminescent probes
Using luminescent conjugated polyelectrolyte probes (LCPs), we demonstrate the possibility to distinguish amyloid-β 1-42 peptide (Aβ1-42) fibril conformations, by analyzing in vitro generated amyloid fibrils of Aβ1-42 formed under quiescent and agitated conditions. LCPs were then shown to resolve such conformational heterogeneity of amyloid deposits in vivo. A diversity of amyloid deposits depending upon morphology and anatomic location was illustrated with LCPs in frozen ex vivo brain sections from a transgenic mouse model (tg-APPswe) of Alzheimers disease. Comparative LCP fluorescence showed that compact-core plaques of amyloid β precursor protein transgenic mice were composed of rigid dense amyloid. A more abundant form of amyloid plaque displayed morphology of a compact center with a protruding diffuse exterior. Surprisingly, the compact center of these plaques showed disordered conformations of the fibrils, and the exterior was composed of rigid amyloid protruding from the disordered ...
http://liu.diva-portal.org/smash/record.jsf?pid=diva2:261471
Missense mutations associated with familial Alzheimers disease in Sweden lead to the production of the amyloid peptide without...Missense mutations associated with familial Alzheimers disease in Sweden lead to the production of the amyloid peptide without...
Production of soluble amyloid peptide precursor (APP) and amyloid peptide (A beta) was measured in CHO cells transfected by the wild-type APP 695 cDNA sequence or by the same sequence carrying missense mutations associated with familial Alzheimers disease in Sweden. Deletion of the C-terminal domain of the protein corresponding to residues 654 to 695 of APP 695 not only inhibited very significantly the internalization of APP at 37 degrees C, but also led to the secretion of an uncleaved APP in the culture medium of CHO cells. This deletion did not affect A beta production from the Swedish APP but was able to inhibit the production of the wild-type APP. These results demonstrate that, in CHO cells, the internalization of the wild-type APP is needed for A beta production, while the production of the amyloid peptide from Swedish APP is independent of the internalization process. ...
https://dial.uclouvain.be/pr/boreal/object/boreal:12161
Perturbations of the Straight Transmembrane alpha-Helical Structure of the Amyloid Precursor Protein Affect Its Processing by...Perturbations of the Straight Transmembrane alpha-Helical Structure of the Amyloid Precursor Protein Affect Its Processing by...
Background: Amyloid- neurotoxicity depends on the specificity of the proteolytic cleavage of the amyloid precursor protein (APP) transmembrane domain. Results: The APP transmembrane -helix is straight in a biological membrane bilayer. Conclusion: The flexibility of APP is key for adapting to the lipid environment and modulating proteolytic processing by -secretase. Significance: The dynamic characterization of APP is expected to rationalize the design of -secretase modulators. The amyloid precursor protein (APP) is a widely expressed type I transmembrane (TM) glycoprotein present at the neuronal synapse. The proteolytic cleavage by -secretase of its C-terminal fragment produces amyloid- (A) peptides of different lengths, the deposition of which is an early indicator of Alzheimer disease. At present, there is no consensus on the conformation of the APP-TM domain at the biological membrane. Although structures have been determined by NMR in detergent micelles, their conformation is markedly ...
https://infoscience.epfl.ch/record/199679
Delineating the physiological actions of the Alzheimers disease Amyloid Precursor Protein family « Styrian Brain Research...Delineating the physiological actions of the Alzheimers disease Amyloid Precursor Protein family « Styrian Brain Research...
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https://en.gehirnforschung.at/blog/2014/03/02/delineating-the-physiological-actions-of-the-alzheimers-disease-amyloid-precursor-protein-family/
Copper Depletion Down-regulates Expression of the Alzheimers Disease Amyloid-β Precursor Protein Gene<...
TY - JOUR. T1 - Copper Depletion Down-regulates Expression of the Alzheimers Disease Amyloid-β Precursor Protein Gene. AU - Bellingham, Shayne A.. AU - Lahiri, Debomoy K.. AU - Maloney, Bryan. AU - La Fontaine, Sharon. AU - Multhaup, Gerd. AU - Camakaris, James. PY - 2004/5/7. Y1 - 2004/5/7. N2 - Alzheimers disease is characterized by the accumulation of amyloid-β peptide, which is cleaved from the amyloid-β precursor protein (APP). Reduction in levels of the potentially toxic amyloid-β has emerged as one of the most important therapeutic goals in Alzheimers disease. Key targets for this goal are factors that affect the regulation of the APP gene. Recent in vivo and in vitro studies have illustrated the importance of copper in Alzheimers disease neuropathogenesis and suggested a role for APP and amyloid-β in copper homeostasis. We hypothesized that metals and in particular copper might alter APP gene expression. To test the hypothesis, we utilized human fibroblasts overexpressing the ...
https://indiana.pure.elsevier.com/en/publications/copper-depletion-down-regulates-expression-of-the-alzheimers-dise
Amyloid Precursor Protein Secretases - beta-Secretase Summary Report | CureHunterAmyloid Precursor Protein Secretases - beta-Secretase Summary Report | CureHunter
Amyloid Precursor Protein Secretases: Endopeptidases that are specific for AMYLOID PROTEIN PRECURSOR. Three secretase subtypes referred to as alpha, beta, and gamma have been identified based upon the region of amyloid protein precursor they cleave.
http://www.curehunter.com/public/keywordSummaryD053829-Amyloid-Precursor-Protein-Secretases-beta-Secretase.do
β-Amyloid precursor protein and tau protein levels are differently regulated in human cerebellum compared to brain regions...
It is well established that the human brain exhibits regional variability in its vulnerability to Alzheimers disease (AD) pathology. We set out to determine if this regional vulnerability is reflected in the expression pattern, or processing, of two key proteins involved in AD pathology, the β-amyloid precursor protein (APP) and tau, by immunoblotting. Our data demonstrate that APP processing and APP protein levels are not different between AD patients and healthy, age-matched subjects, but that levels of mature APP are greatly reduced in cerebellum compared to regions of the brain most vulnerable to AD, entorhinal cortex and hippocampus. In addition, protein levels of tau are significantly reduced in cerebellum compared to all other human brain regions examined. Unexpectedly, protein levels of glycogen synthase kinase 3 (GSK3), a major tau kinase, are at their lowest in hippocampus. The observations demonstrate that both mature APP as well as total APP and tau protein levels are greatly reduced in
https://www.neuroscience.ox.ac.uk/publications/622618
APP Metabolism Regulates Tau Proteostasis in Human Cerebral Cortex NeuronsAPP Metabolism Regulates Tau Proteostasis in Human Cerebral Cortex Neurons
Accumulation of A beta peptide fragments of the APP protein and neurofibrillary tangles of the microtubule-associated protein tau are the cellular hallmarks of Alzheimers disease (AD). To investigate the relationship between APP metabolism and tau protein levels and phosphorylation, we studied human-stem-cell-derived forebrain neurons with genetic forms of AD, all of which increase the release of pathogenic A beta peptides. We identified marked increases in intracellular tau in genetic forms of AD that either mutated APP or increased its dosage, suggesting that APP metabolism is coupled to changes in tau proteostasis. Manipulating APP metabolism by beta-secretase and gamma-secretase inhibition, as well as gamma-secretase modulation, results in specific increases and decreases in tau protein levels. These data demonstrate that APP metabolism regulates tau proteostasis and suggest that the relationship between APP processing and tau is not mediated solely through extracellular A beta signaling to ...
http://su.diva-portal.org/smash/record.jsf?pid=diva2%3A817545&c=1&searchType=SIMPLE&language=en&query=&af=%5B%5D&aq=%5B%5B%7B%22personId%22%3A%22thand%22%7D%5D%5D&aq2=%5B%5B%5D%5D&aqe=%5B%5D&noOfRows=50&sortOrder=author_sort_asc&sortOrder2=title_sort_asc&onlyFullText=false&sf=all
Frontiers | Alzheimers Disease and Hippocampal Adult Neurogenesis; Exploring Shared Mechanisms | NeuroscienceFrontiers | Alzheimers Disease and Hippocampal Adult Neurogenesis; Exploring Shared Mechanisms | Neuroscience
New neurons incorporate into the granular cell layer of the dentate gyrus throughout life. Neurogenesis is modulated by behavior and plays a major role in hippocampal plasticity. Along with older mature neurons, new neurons structure the dentate gyrus and determine its function. Recent data suggest that the level of hippocampal neurogenesis is substantial in the human brain, suggesting that neurogenesis may have important implications for human cognition. In support of that, impaired neurogenesis compromises hippocampal function and plays a role in cognitive deficits in Alzheimers disease mouse models. We review current work suggesting that neuronal differentiation is defective in Alzheimers disease, leading to dysfunction of the dentate gyrus. Additionally, alterations in critical signals regulating neurogenesis, such as presenilin-1, Notch 1, soluble amyloid precursor protein, CREB, and β-catenin underlie dysfunctional neurogenesis in Alzheimers disease. Lastly, we discuss the detectability of
https://www.frontiersin.org/articles/10.3389/fnins.2016.00178/full
Axonal transport, amyloid precursor protein, kinesin-1, and the processing apparatus: Revisited<...
TY - JOUR. T1 - Axonal transport, amyloid precursor protein, kinesin-1, and the processing apparatus. T2 - Revisited. AU - Lazarov, Orly. AU - Morfini, Gerardo A.. AU - Lee, Edward B.. AU - Farah, Mohamed H.. AU - Szodorai, Anita. AU - DeBoer, Scott R.. AU - Koliatsos, Vassilis E.. AU - Kins, Stefan. AU - Lee, Virginia M.Y.. AU - Wong, Philip C.. AU - Price, Donald L.. AU - Brady, Scott T.. AU - Sisodia, Sangram S.. N1 - Copyright: Copyright 2008 Elsevier B.V., All rights reserved.. PY - 2005/3/2. Y1 - 2005/3/2. N2 - The sequential enzymatic actions of β-APP cleaving enzyme 1 (BACE1), presenilins (PS), and other proteins of the γ-secretase complex liberate β-amyloid (Aβ) peptides from larger integral membrane proteins, termed β-amyloid precursor proteins (APPs). Relatively little is known about the normal function(s) of APP or the neuronal compartment(s) in which APP undergoes proteolytic processing. Recent studies have been interpreted as consistent with the idea that APP serves as a ...
https://jhu.pure.elsevier.com/en/publications/axonal-transport-amyloid-precursor-protein-kinesin-1-and-the-proc-6
Brain Ischemia: Alzheimers Disease Mechanisms - Nova Science PublishersBrain Ischemia: Alzheimers Disease Mechanisms - Nova Science Publishers
This new book presents a summary of Alzheimers disease-related ischemic protein changes and gene expression as risk factors for the late-onset of sporadic Alzheimers disease, and their role in Alzheimers disease ischemic etiology. Ischemic brain changes were noted in the staining of different parts of an amyloid protein precursor, presenilin 1 and 2, tau protein, alfa-synuclein, and apolipoproteins A1, E and J.. Current advances in understanding the ischemic etiology of Alzheimers disease has revealed dysregulation of Alzheimers disease-associated genes including presenilin 1 and 2, β-secretase, amyloid protein precursor, apoptosis, autophagy, mitophagy, and tau protein. This book presents the relationship between these genes, dysregulated by cerebral ischemia, and the cellular and tissue neuropathology characteristic of Alzheimers disease. This book draws attention to the latest research confirming the theory that Alzheimers disease-related proteins and genes play an important role in ...
https://novapublishers.com/shop/brain-ischemia-alzheimers-disease-mechanisms/?add_to_wishlist=24882
Neurodegeneration and Neurogenesis: Focus on Alzheimers Disease | BenthamScienceNeurodegeneration and Neurogenesis: Focus on Alzheimers Disease | BenthamScience
Title: Neurodegeneration and Neurogenesis: Focus on Alzheimers Disease. VOLUME: 3 ISSUE: 1. Author(s):David A. Greenberg and Kunlin Jin. Affiliation:Buck Institute for Age Research,8001 Redwood Boulevard, Novato, CA 94945, USA.. Keywords:Neurodegeneration, neurogenesis, neuronal precursor cells, stem cells, hippocampus, dentate gyrus. Abstract: Neurogenesis, or the production of new neurons from neuronal precursor cells, is a normal phenomenon in the adult brain, and is accentuated by brain injury. Forms of injury associated with increased neurogenesis include both acute (e.g., stroke) and chronic neurodegenerations. Studies on human postmortem material and transgenic mice overexpressing amyloid precursor protein mutations found in familial Alzheimers disease (AD) suggest that AD is associated with enhanced neurogenesis. However, the mechanism responsible for this effect is unknown, as is what influence it may have on the clinical course of murine or human AD. If AD leads to the production of ...
http://www.eurekaselect.com/56748/article
Anti-Human Presenilin-1 Antibody | Human Presenilin-1 Antibody | Presenilin-1 AntibodyAnti-Human Presenilin-1 Antibody | Human Presenilin-1 Antibody | Presenilin-1 Antibody
TumorPortal
The protein encoded by this gene is a member of the Fe65 protein family. It is an adaptor protein localized in the nucleus. It interacts with the Alzheimers disease amyloid precursor protein (APP), transcription factor CP2/LSF/LBP1 and the low-density lipoprotein receptor-related protein. APP functions as a cytosolic anchoring site that can prevent the gene products nuclear translocation. This encoded protein could play an important role in the pathogenesis of Alzheimers disease. It is thought to regulate transcription. Also it is observed to block cell cycle progression by downregulating thymidylate synthase expression. Multiple alternatively spliced transcript variants encoding different isoforms have been described for this gene ...
http://www.tumorportal.org/view?geneSymbol=APBB1
UBE1C - WikipediaUBE1C - Wikipedia
NEDD8-activating enzyme E1 catalytic subunit is a protein that in humans is encoded by the UBA3 gene.[5][6] The modification of proteins with ubiquitin is an important cellular mechanism for targeting abnormal or short-lived proteins for degradation. Ubiquitination involves at least three classes of enzymes: ubiquitin-activating enzymes, or E1s, ubiquitin-conjugating enzymes, or E2s, and ubiquitin-protein ligases, or E3s. This gene encodes a member of the E1 ubiquitin-activating enzyme family. The encoded enzyme associates with AppBp1, an amyloid beta precursor protein binding protein, to form a heterodimer, and then the enzyme complex activates NEDD8, a ubiquitin-like protein, which regulates cell division, signaling and embryogenesis. Multiple alternatively spliced transcript variants encoding distinct isoforms have been found for this gene.[6] This enzyme contains an E2 binding domain, which resembles ubiquitin, and recruits the catalytic core of the E2 enzyme UBE2M (Ubc12) in a similar ...
https://en.wikipedia.org/wiki/UBE1C
USE OF BIOMARKERS OF ALZHEIMERS DISEASE FOR DIAGNOSTIC TESTS AND DRUG SCREENING - Patent applicationUSE OF BIOMARKERS OF ALZHEIMERS DISEASE FOR DIAGNOSTIC TESTS AND DRUG SCREENING - Patent application
0037]The term amyloid-β (or Aβ) as used herein has the standard meaning understood in the art. The full length beta amyloid precursor protein (APP) occurs in nature in several variants, up to 770 amino acids in length, with other characterized species including variants 695, 639, 574, 547, 484, 352, 327 and 305 amino acids in length. Amyloid-β polypeptides may be of various lengths, including 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, ...
http://www.patentsencyclopedia.com/app/20090104629
1taw - Proteopedia, life in 3D1taw - Proteopedia, life in 3D
The crystal structures of the inhibitor domain of Alzheimers amyloid beta-protein precursor (APPI) complexed to bovine chymotrypsin (C-APPI) and trypsin (T-APPI) and basic pancreatic trypsin inhibitor (BPTI) bound to chymotrypsin (C-BPTI) have been solved and analyzed at 2.1 A, 1.8 A, and 2.6 A resolution, respectively. APPI and BPTI belong to the Kunitz family of inhibitors, which is characterized by a distinctive tertiary fold with three conserved disulfide bonds. At the specificity-determining site of these inhibitors (P1), residue 15(I)4 is an arginine in APPI and a lysine in BPTI, residue types that are counter to the chymotryptic hydrophobic specificity. In the chymotrypsin complexes, the Arg and Lys P1 side chains of the inhibitors adopt conformations that bend away from the bottom of the binding pocket to interact productively with elements of the binding pocket other than those observed for specificity-matched P1 side chains. The stereochemistry of the nucleophilic hydroxyl of Ser 195 ...
http://proteopedia.org/wiki/index.php/1taw
RCSB PDB - 1CA0: BOVINE CHYMOTRYPSIN COMPLEXED TO APPI Methods Report PageRCSB PDB - 1CA0: BOVINE CHYMOTRYPSIN COMPLEXED TO APPI Methods Report Page
1CA0: Crystal structures of bovine chymotrypsin and trypsin complexed to the inhibitor domain of Alzheimers amyloid beta-protein precursor (APPI) and basic pancreatic trypsin inhibitor (BPTI): engineering of inhibitors with altered specificities.
http://www.rcsb.org/pdb/explore/materialsAndMethods.do?structureId=1CA0
Cellular Mechanisms for the Release of Exosomes Containing the Amyloid Precursor ProteinCellular Mechanisms for the Release of Exosomes Containing the Amyloid Precursor Protein
The Amyloid Precursor Protein (APP) is a transmembrane protein whose cleavage results in toxic Aß fragment identified as the major constituent in the amyloid plaques of Alzheimers Disease. Recent evidence has shown that fragments of APP including its intracellular domain are secreted into the extracellular space, possibly via the formation and release of extracellular vesicles called exosomes, which are derived from endosomes. in the Drosophila model, we have manipulated specific components of the membrane trafficking machinery predicted to be involved in APP traffic, and measured their effects on in vivo APPeGFP exosome secretion using fluorescence quantification. We targeted the Vps35, Snx1, and Snx3 components of the endosomal sorting complex called Retromer (which is implicated in Alzheimers Disease), and the GTPase Rab11 which has been implicated in exocytosis. Our results indicate that Rab11 and the Snx1 are required for exosome release while Snx3 and Vps35, perhaps working together ...
http://bir.brandeis.edu/handle/10192/25270
Presenilin-1 mutations of leucine 166 equally affect the generation of the Notch and APP intracellular domains independent of...
The Alzheimers disease (AD)-associated presenilin (PS) proteins are required for the γ-secretase cleavages of the β-amyloid precursor protein and the site 3 (S3) protease cleavage of Notch. These intramembrane cleavages release amyloid-β peptide (Aβ), including the pathogenic 42-aa variant (Aβ(42)), as well as the β-amyloid precursor protein and the Notch intracellular domains (AICD, NICD). Whereas Aβ is generated by endoproteolysis in the middle of the transmembrane domain, AICD and NICD are generated by cleavages at analogous positions close to the cytoplasmic border of the transmembrane domain. Numerous mutations causing familial AD (FAD) that all cause increased production of Aβ(42) have been found in the PS1 gene. Here we have investigated the previously uncharacterized, very aggressive FAD mutation L166P that causes onset of AD in adolescence. Strikingly, the PS1 L166P mutation not only induces an exceptionally high increase of Aβ(42) production but also impairs NICD production ...
https://www.biochemie.abi.med.uni-muenchen.de/publications/article/pub_2002_005.html
APP gene - Genetics Home Reference
The Italian type and Arctic type are also caused by changes to glutamic acid at position In the Italian type, glutamic acid is replaced with the amino acid lysine written as Glu22Lys or E22K and in the Arctic type, glutamic acid is replaced with the amino acid glycine written as Glu22Gly or E22G.. More than 50 different mutations in the APP gene can cause early-onset Alzheimer disease, which begins before age Controlling neural stem cell division within the adult subventricular zone: The amyloid hypothesis of Alzheimers disease: These mutations change single amino acids in the amyloid precursor protein. When these protein fragments are released from the cell, they can accumulate in the brain and form clumps called amyloid plaques. ...
http://mopscafe.com/app/dejting-app-gene.html
Alzheimers disease - WikipediaAlzheimers disease - Wikipedia
In 1991, the amyloid hypothesis postulated that extracellular amyloid beta (Aβ) deposits are the fundamental cause of the disease.[54][55] Support for this postulate comes from the location of the gene for the amyloid precursor protein (APP) on chromosome 21, together with the fact that people with trisomy 21 (Down Syndrome) who have an extra gene copy almost universally exhibit at least the earliest symptoms of AD by 40 years of age.[56][57] Also, a specific isoform of apolipoprotein, APOE4, is a major genetic risk factor for AD. While apolipoproteins enhance the breakdown of beta amyloid, some isoforms are not very effective at this task (such as APOE4), leading to excess amyloid buildup in the brain.[58] Further evidence comes from the finding that transgenic mice that express a mutant form of the human APP gene develop fibrillar amyloid plaques and Alzheimers-like brain pathology with spatial learning deficits.[59]. An experimental vaccine was found to clear the amyloid plaques in early ...
https://en.m.wikipedia.org/wiki/Alzheimer%27s
British Library EThOS: Investigations of age- and plaque-related learning deficits in PDAPP mice and evaluations of anti...British Library EThOS: Investigations of age- and plaque-related learning deficits in PDAPP mice and evaluations of anti...
A cross-sectional and a longitudinal design were employed to address whether PDAPP mice exhibit any plaque-related learning deficit. Firstly, the cross-sectional study indicated that PDAPP mice simultaneously displayed an early (plaque-independent) and age-related learning impairment. Further analysis showed that the age-related learning deficit was highly correlated with plaque burden in the hippocampus of aged PDAPP mice, suggesting that amyloid plaques play a very important role in memory loss of AD. Second, the longitudinal study showed that the same PDAPP mice exhibited significant age-related learning deficits in trials to criterion and learning capacity tasks when they aged. Interestingly, cued navigation and object recognition in both cross-sectional and longitudinal studies were unaffected, indicating normal sensorimotor function and recognition memory of PDAPP mice. The longitudinal study further showed that the age-related learning impairment was significantly correlated with ...
http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.642779
APP mutations in the Aβ coding region are associated with abundant cerebral deposition of Aβ38<...
TY - JOUR. T1 - APP mutations in the Aβ coding region are associated with abundant cerebral deposition of Aβ38. AU - Moro, Maria Luisa. AU - Giaccone, Giorgio. AU - Lombardi, Raffaella. AU - Indaco, Antonio. AU - Uggetti, Andrea. AU - Morbin, Michela. AU - Saccucci, Stefania. AU - Di Fede, Giuseppe. AU - Catania, Marcella. AU - Walsh, Dominic M.. AU - Demarchi, Andrea. AU - Rozemuller, Annemieke. AU - Bogdanovic, Nenad. AU - Bugiani, Orso. AU - Ghetti, Bernardino. AU - Tagliavini, Fabrizio. PY - 2012/12. Y1 - 2012/12. N2 - Aβ is the main component of amyloid deposits in Alzheimer disease (AD) and its aggregation into oligomers, protofibrils and fibrils is considered a seminal event in the pathogenesis of AD. Aβ with C-terminus at residue 42 is the most abundant species in parenchymal deposits, whereas Aβ with C-terminus at residue 40 predominates in the amyloid of the walls of large vessels. Aβ peptides with other C-termini have not yet been thoroughly investigated. We analysed Aβ38 in ...
https://moh-it.pure.elsevier.com/en/publications/app-mutations-in-the-a%CE%B2-coding-region-are-associated-with-abundan
Senile plaques - WikipediaSenile plaques - Wikipedia
Concentrated in the synapse of neurons is an amyloid precursor protein (APP) that extends across the plasma membrane. A portion of this protein contains an Aβ peptide sequence. This region comprises part of the DNA segment spanning APP that codes for proteins.[10]. In the formation of senile plaques, Aβ is cleaved from the amyloid precursor protein. Although three enzymes can process APP, only β-(beta) and γ-(gamma) secretase are directly involved in the formation of senile plaques. β-secretase (BACE) is a protease enzyme that cleaves proteins and peptides. This protease cleaves APP to further expose the carboxyl terminal fragments of Aβ. After the bulk of APP is released by this process, γ-secretase cleaves the remaining carboxyl fragments on the transmembrane domain. The sequential actions of γ-secretase following BACE activity results in Aβ protein fragments (amyloid beta) that are released into the extracellular space.[10] Eventually, the accumulation of amyloid beta outside of ...
https://en.m.wikipedia.org/wiki/Senile_plaque
New animal models of Alzheimers disease | The Florey - Institute of Neuroscience and Mental HealthNew animal models of Alzheimers disease | The Florey - Institute of Neuroscience and Mental Health
Alzheimers disease (AD) is the most common age-related dementia, with the number of affected individuals expected to exceed 100 million worldwide by 2050. In Australia, Alzheimers disease is the third leading cause of death behind heart disease and cancer. Despite the significance of this disease there are currently no disease modifying drugs to treat Alzheimers disease.. One of the pathological hallmarks of Alzheimers disease is the cerebral deposition of plaques composed of Amyloid-beta (Aß) peptide. Aß is produced by sequential proteolytic cleavage of the ubiquitously expressed integral-membrane protein, amyloid ß-protein precursor. The Aß released typically ranges from 38 to 43 amino acids in length due to imprecise cleavage. Peptides Aß1-40 and Aß1-42 are two of the most common forms and have received the majority of research attention. Clearance of Aß is slowed in cerebrospinal fluid from Alzheimers disease patients, which likely contributes to its pathological deposition. The ...
https://www.florey.edu.au/rapid-animal-models-alzheimer%E2%80%99s-disease
The PI3K-Akt-mTOR pathway regulates Aβ oligomer induced neuronal cell cycle events | Molecular Neurodegeneration | Full TextThe PI3K-Akt-mTOR pathway regulates Aβ oligomer induced neuronal cell cycle events | Molecular Neurodegeneration | Full Text
Accumulating evidence suggests that neurons prone to degeneration in Alzheimers Disease (AD) exhibit evidence of re-entry into an aberrant mitotic cell cycle. Our laboratory recently demonstrated that, in a genomic amyloid precursor protein (APP) mouse model of AD (R1.40), neuronal cell cycle events (CCEs) occur in the absence of beta-amyloid (Aβ) deposition and are still dependent upon the amyloidogenic processing of the amyloid precursor protein (APP). These data suggested that soluble Aβ species might play a direct role in the induction of neuronal CCEs. Here, we show that exposure of non-transgenic primary cortical neurons to Aβ oligomers, but not monomers or fibrils, results in the retraction of neuronal processes, and induction of CCEs in a concentration dependent manner. Retraction of neuronal processes correlated with the induction of CCEs and the Aβ monomer or Aβ fibrils showed only minimal effects. In addition, we provide evidence that induction of neuronal CCEs are autonomous to primary
https://molecularneurodegeneration.biomedcentral.com/articles/10.1186/1750-1326-4-14/figures/6
OptimAbᵀᴹ Beta-Amyloid 17-24 , Monoclonal Antibody, purifiedOptimAbᵀᴹ Beta-Amyloid 17-24 , Monoclonal Antibody, purified
Antibodies , OptimAb Antibodies , OptimAbᵀᴹ Beta-Amyloid 17-24 , Monoclonal Antibody, purified; Beta-Amyloid forms are deposited in the CNS of patients with Alzheimer s disease and Down s syndrome. Biochemical analysis of the amyloid peptides isolated from Alzheimer s disease brain indicates that Beta-Amyloid (1-42) is the principal species associated with senile plaque amyloids, while Beta-Amyloid (1-40) is more abundant in cerebrovascular amyloid deposits. Both result from the cleavage of Amyloid Precursor Protein (APP) by secretases. The mAb 4G8 reacts to the abnormally processed isoforms, as well as precursor forms.; Host:MouseClone: 4G8Isotype: IgG2bReactivity: Human, MouseImmunogen: This antibody is reactive to residues 17-24 of Beta-Amyloid. The epitope lies within amino acids 18-22 of Beta-Amyloid (VFFAE)Concentration:1 mg/mLFormulation:PBS (no preservatives); The Ab was purified on Protein GApplications:The Ab is effective in immunoblotting (WB),
https://anaspec.com/products/product.asp?id=58695
MH84 improves mitochondrial dysfunction in a mouse model of early Alzheimers disease | Alzheimers Research & Therapy | Full...MH84 improves mitochondrial dysfunction in a mouse model of early Alzheimers disease | Alzheimers Research & Therapy | Full...
Current approved drugs for Alzheimers disease (AD) only attenuate symptoms, but do not cure the disease. The pirinixic acid derivate MH84 has been characterized as a dual gamma-secretase/proliferator activated receptor gamma (PPARγ) modulator in vitro. Pharmacokinetic studies in mice showed that MH84 is bioavailable after oral administration and reaches the brain. We recently demonstrated that MH84 improved mitochondrial dysfunction in a cellular model of AD. In the present study, we extended the pharmacological characterization of MH84 to 3-month-old Thy-1 AβPPSL mice (harboring the Swedish and London mutation in human amyloid precursor protein (APP)) which are characterized by enhanced AβPP processing and cerebral mitochondrial dysfunction, representing a mouse model of early AD. Three-month-old Thy-1 AβPPSL mice received 12 mg/kg b.w. MH84 by oral gavage once a day for 21 days. Mitochondrial respiration was analyzed in isolated brain mitochondria, and mitochondrial membrane potential and ATP
https://alzres.biomedcentral.com/articles/10.1186/s13195-018-0342-6
Minocycline blocks c-terminal fragments of amyloid precursor protein-induced neurotoxicity by inhibition of cytochrome c...Minocycline blocks c-terminal fragments of amyloid precursor protein-induced neurotoxicity by inhibition of cytochrome c...
Minocycline is a second-generation tetracycline that effectively crosses the blood-brain barrier. It has remarkable neuroprotective qualities in models of cerebral ischaemia, traumatic brain injury, Huntingtons and Parkinsons diseases. However, there is no evidence about neuroprotective effects of minocycline on AD. Alzheimers disease (AD) is a neurodegenerative disorder characterized neuropathologically by the presence of neuritic plaques containing amyloid fibrils and neurofibrillary tangles whose main component is paired helical filament composed of hyperphosphorylated tau. There are numerous lines of evidence that some of the neurotoxicity associated with AD is due to proteolytic fragments of the amyloid precursor protein (APP). In this study, it was found out that minocycline reduces neurotoxicity induced by various C-terminal fragments of APP through inhibition of cytochrome c release and caspase-12 activation.
http://ijpr.sbmu.ac.ir/article_214.html
Identification of novel N… - Göteborgs universitetIdentification of novel N… - Göteborgs universitet
Alzheimers disease (AD) is a progressive neurodegenerative disorder of the central nervous system. Two pathological hallmarks in the brain of AD patients are neurofibrillary tangles and senile plaques. The plaques consist mainly of beta-amyloid (Abeta) peptides that are produced from the amyloid precursor protein (APP), by sequential cleavage by beta- and gamma-secretase. Most previous studies have been focused on the C-terminal fragments of APP, where the Abeta sequence is localized. The purpose of this study was to search for N-terminal fragments of APP in cerebrospinal fluid (CSF) using mass spectrometry (MS). By using immunoprecipitation (IP) combined with matrix-assisted laser desorption/ionization time-of-flight MS as well as nanoflow liquid chromatography coupled to high resolution tandem MS we were able to detect and identify six novel N-terminal APP fragments [APP((18-119)), APP((18-121)), APP((18-122)), APP((18-123)), APP((18-124)) and APP((18-126))], having molecular masses of ...
https://www.gu.se/forskning/publikation?publicationId=98777
Beta Amyloid [1-40] Peptide | AbbiotecBeta Amyloid [1-40] Peptide | Abbiotec
Beta-amyloid production results from cleavage in the extracellular domain of APP by the beta-secretase (BACE1) , which results in the production of the APP C-terminal fragment C99. This fragment is further cleaved by the gamma-secretase at residues 40-42 to produce beta-amyloid 40 and 42 peptides. Beta-amyloid aggregation and neuritic plaque formation are pathologic hallmarks of Alzheimer disease. This peptide corresponds to the human beta-amyloid 1-40 peptide ...
http://abbiotec.com/peptides/beta-amyloid-1-40-peptide
Alzheimers disease - Simple English Wikipedia, the free encyclopediaAlzheimers disease - Simple English Wikipedia, the free encyclopedia
In different parts of the of cell including the outermost part of the cell membrane, chemicals called enzymes snip the APP into small pieces. These enzymes that do the snipping are alpha-secretase, beta-secretase, and gamma-secretase. Depending on which enzyme is doing the snipping and what parts of the APP are snipped, two different things can happen. One that is helpful and one that causes the formation of beta-amyloid plaques. The plaques are formed when beta-secretase snips the APP molecule at one end of the beta-amyloid peptide, releasing sAPPβ from the cell. Gamma-secretase then cuts the pieces of APP that is left and, still sticking out of the neurons membrane, at the other end of the beta-amyloid peptide. After this snipping the beta-amyloid peptide is released into the space outside the neuron and begins to stick to other beta-amyloid peptides. These pieces stick together to form oligomers. Different oligomers of various sizes are now floating around in the spaces between the neurons, ...
https://simple.wikipedia.org/wiki/Alzheimer%27s_disease
Re-evaluation of soluble APP-α and APP-β in cerebrospinal fluid as potential biomarkers for early diagnosis of dementia...Re-evaluation of soluble APP-α and APP-β in cerebrospinal fluid as potential biomarkers for early diagnosis of dementia...
Because soluble (or secreted) amyloid precursor protein-β (sAPPβ) and -α (sAPPα) possibly reflect pathological features of Alzheimers disease (AD), they are potential biomarker candidates for dementia disorders, including AD and mild cognitive impairment (MCI) due to AD (MCI-AD). However, controversial results have been reported regarding their alterations in the cerebrospinal fluid (CSF) of AD and MCI-AD patients. In this study, we re-assessed the utility of sAPPα and sAPPβ in CSF as diagnostic biomarkers of dementia disorders. We used a modified and sensitive detection method to analyze sAPPs levels in CSF in four groups of patients: AD (N = 33), MCI-AD (N = 17), non-AD dementia (N = 27), and disease controls (N = 19). Phosphorylated tau (p-tau), total tau, and Aβ42 were also analyzed using standard methods. A strong correlation was observed between sAPPα and sAPPβ, consistent with previous reports. Both sAPPα and sAPPβ were highly correlated with p-tau and total tau, suggesting that sAPPs
https://biomarkerres.biomedcentral.com/articles/10.1186/s40364-017-0108-5/figures/4
Discovery and Evaluation of BMS-708163, a Potent, Selective and Orally Bioavailable gamma-Secretase Inhibitor<...
TY - JOUR. T1 - Discovery and Evaluation of BMS-708163, a Potent, Selective and Orally Bioavailable gamma-Secretase Inhibitor. AU - Gillman, K.W.. AU - Starrett, J.E.. AU - Parker, M.F.. AU - Xie, K.. AU - Bronson, J.J.. AU - Marcin, L.R.. AU - McElhone, K.E.. AU - Bergstrom, C.P.. AU - Mate, R.A.. AU - Williams, Richard. AU - Meredith, J.E.. AU - Burton, C.R.. AU - Barten, D.M.. AU - Toyn, J.H.. AU - Roberts, S.B.. AU - Lentz, K.A.. AU - Houston, J.G.. AU - Zaczek, R.. AU - Albright, C.F.. AU - Decicco, C.P.. AU - Macor, J.E.. AU - Olson, R.E.. PY - 2010/6/10. Y1 - 2010/6/10. N2 - During the course of our research efforts to develop a potent and selective gamma-secretase inhibitor for the treatment of Alzheimers disease, we investigated a series of carboxamide-substituted sulfonamides. Optimization based on potency, Notch/amyloid-beta precursor protein selectivity, and brain efficacy after oral dosing led to the discovery of 4 (BMS-708163). Compound 4 is a potent inhibitor of gamma-secretase ...
https://pure.qub.ac.uk/en/publications/discovery-and-evaluation-of-bms-708163-a-potent-selective-and-ora
Patent US5981208 - Diagnostic assay for Alzheimers disease based on the proteolysis of the ... - Google PatentsPatent US5981208 - Diagnostic assay for Alzheimers disease based on the proteolysis of the ... - Google Patents
A method useful in the diagnosis of Alzheimers Disease in a patient in which an amyloid protein precursor (APP) substrate is combined with a sample of cerebrospinal fluid or blood obtained from the patient to be tested, and poteolytic cleavage of the APP substrate is detected. The absence of detectable proteolytic cleavage, or the detection of a substantially lesser degree of proteolytic cleavage, in the presence of the patients sample compared to that detected when an APP substrate is combined with test samples from control individuals, indicates affliction with Alzheimers Disease. Convenient test reagents and kits for aiding the diagnosis of Alzheimers Disease are provided, such as comprising an APP substrate and immunoreagents for detecting a fragment formed by proteolytic cleavage as well as chromogenic APP substrates.
http://www.google.com.au/patents/US5981208
Projektansicht | Alzheimer Forschung Initiative e.V. (AFI)Projektansicht | Alzheimer Forschung Initiative e.V. (AFI)
In this study we analysed the influence of the Amyloid precursor protein (APP) interacting proteins on APP function, trafficking and processing in neuronal cells. Firstly, we examined the proposed interaction of APP, APLP1 and APLP2 with conventional kinesin. Previous studies reported that the cytoplasmic domain of APP exhibits high affinity binding with kinesin light chain (KLC). In context of this research project we provide evidence from GST-pull down analyses and co-immunoprecipitation studies that KLC does not interact directly with the cytoplasmic tail of APP, APLP1 or APLP2. Further, quantitative confocal analyses revealed that mutant APP lacking the APP intracellular domain were sorted, similar to wildtyp APP, to both, axons and dendrites. Thus, the intracellular domain and cytosolic interaction partners of APP/APLPs are not essential to mediate polarized transport in neurons. As the sorting of APP and APLP2 depend in non neuronal cells on the presence of the basolateral sorting signal ...
https://www.alzheimer-forschung.de/forschung/forschungsprojekte/projektansicht/foerderprojekt/show/Projekt/regulierung-des-app-aplp1-und-aplp2-transports/
Functional proteomic analysis of altered protein signaling modules in Alzheimers disease :: University of Southern California...
Neuritic plaques comprised of amyloid ß (Aß) are one of the primary neuropathological hallmarks of Alzheimers disease (AD). However, Aß plaque deposition is preceded by aberrations of the endosomal/lysosomal system, including abnormally enlarged endosomal compartments, accumulation of protease-resistant proteins, and atypical activation of the lysosomal system. The functional mechanisms accounting for these abnormalities have not yet been delineated. Towards our goal of identifying the proteins whose dysfunction contributes to the development of endosomal/lysosomal pathology in AD, we have found that: 1) proteins implicated in regulating late endosomal trafficking are among the targets of oxidation (carbonylation) in the brain of a presenilin 1/amyloid precursor protein (PS1/APP) transgenic mouse model of AD; 2) reduced neuronal expression of synaptic membrane protein HNK-1/NCAM is associated with Aß pathology in models of Aß deposition in cell culture and an amyloid precursor protein ...
http://digitallibrary.usc.edu/cdm/compoundobject/collection/p15799coll127/id/329545/rec/20
Functional proteomic analysis of altered protein signaling modules in Alzheimers disease :: University of Southern California...
Neuritic plaques comprised of amyloid ß (Aß) are one of the primary neuropathological hallmarks of Alzheimers disease (AD). However, Aß plaque deposition is preceded by aberrations of the endosomal/lysosomal system, including abnormally enlarged endosomal compartments, accumulation of protease-resistant proteins, and atypical activation of the lysosomal system. The functional mechanisms accounting for these abnormalities have not yet been delineated. Towards our goal of identifying the proteins whose dysfunction contributes to the development of endosomal/lysosomal pathology in AD, we have found that: 1) proteins implicated in regulating late endosomal trafficking are among the targets of oxidation (carbonylation) in the brain of a presenilin 1/amyloid precursor protein (PS1/APP) transgenic mouse model of AD; 2) reduced neuronal expression of synaptic membrane protein HNK-1/NCAM is associated with Aß pathology in models of Aß deposition in cell culture and an amyloid precursor protein ...
http://digitallibrary.usc.edu/cdm/compoundobject/collection/p15799coll127/id/329545/rec/10
Amyloid beta-Protein (Human, 34-40) Antiserum (50 µL vial)Amyloid beta-Protein (Human, 34-40) Antiserum (50 µL vial)
Product Name: Amyloid beta-Protein (Human, 34-40) Antiserum (50 ul vial) Product Number: NAB-14356-v Synonym(s): Amyloid beta-Protein (1-40) Specific Antiserum (Rabbit) Antiserum Application: Our undiluted antisera are suitable for immuno-histochemical use, for application to radioimmunoassay (RIA), or other non-isotop
https://vivitide.com/products/nab-14356-v
Activation of GSK-3 and phosphorylation of CRMP2 in transgenic mice expressing APP intracellular domain | JCBActivation of GSK-3 and phosphorylation of CRMP2 in transgenic mice expressing APP intracellular domain | JCB
The biologic relevance of AICD to APP physiology or AD pathology has been proposed, but in vivo evidence that supports the hypothesis has been lacking. The current study was aimed at examining this hypothesis by expressing AICD postnatally and selectively in the forebrain and hippocampal regions of mouse brain. Here, we first show that AICD is present in brain membranes from normal control mice and can be detected by Western blot alone. We further demonstrate that the transgenic mice that were generated in this study express AICD at levels that are similar to those found in APP transgenic mice with FAD mutation, which are two- to threefold higher than in nontransgenic mice. These data strongly support the validity of our mouse model, which was verified further by observing increased expression of KAI1 gene in transgenic mice. Finally, we present evidence that the AICD transgenic mice display robust changes in GSK-3 signaling, which supports an in vivo role for AICD.. The finding that an ...
http://jcb.rupress.org/content/171/2/327.long
SEPT8 modulates β-amyloidogenic processing of APP via affecting the sorting and accumulation of BACE1 | Journal of Cell ScienceSEPT8 modulates β-amyloidogenic processing of APP via affecting the sorting and accumulation of BACE1 | Journal of Cell Science
Dysfunction and loss of synapses are early pathogenic events in Alzheimers disease (AD). A central step in the generation of toxic amyloid-β (Aβ) peptides is the cleavage of amyloid precursor protein (APP) by β-site APP cleaving enzyme (BACE1). Here, we have elucidated whether down-regulation of septin (SEPT) protein family members, which are implicated in synaptic plasticity and vesicular trafficking, affects APP processing and Aβ generation. SEPT8 was found to reduce soluble APPβ and Aβ levels in neuronal cells via a post-translational mechanism leading to the decreased levels of BACE1 protein. In human temporal cortex, we identified alterations in the expression of specific SEPT8 transcript variants in relation to AD-related neurofibrillary pathology. These changes associated with altered β-secretase activity. We also discovered that the overexpression of a specific AD-associated SEPT8 transcript variant increased the levels of BACE1 and Aβ in neuronal cells. These changes were ...
http://jcs.biologists.org/content/early/2016/04/13/jcs.185215
Frontiers | Ovarian Hormone-Dependent Effects of Dietary Lipids on APP/PS1 Mouse Brain | Frontiers in Aging NeuroscienceFrontiers | Ovarian Hormone-Dependent Effects of Dietary Lipids on APP/PS1 Mouse Brain | Frontiers in Aging Neuroscience
The formation of senile plaques through amyloid-β peptide (Aβ) aggregation is a hallmark of Alzheimers disease (AD). Irrespective of its actual role in the synaptic alterations and cognitive impairment associated with AD, different therapeutic approaches have been proposed to reduce plaque formation. In rodents, daily intake of omega-3 (n-3) long-chain polyunsaturated fatty acids (LC-PUFAs) is required for neural development, and there is experimental and epidemiological evidence that their inclusion in the diet has positive effects on several neurodegenerative diseases. Similarly, estradiol appears to reduce senile plaque formation in primary mouse cell cultures, human cortical neurons and mouse AD models, and it prevents Aβ toxicity in neural cell lines. We previously showed that differences in dietary n-6/n-3 LC-PUFAs ratios modify the lipid composition in the cerebral cortex of female mice and the levels of amyloid precursor protein (APP) in the brain. These effects depended in part on the
https://www.frontiersin.org/articles/10.3389/fnagi.2019.00346/full
JCI - NSAIDs and enantiomers of flurbiprofen target γ-secretase and lower Aβ42 in vivoJCI - NSAIDs and enantiomers of flurbiprofen target γ-secretase and lower Aβ42 in vivo
Epidemiologic studies demonstrate that long-term use of NSAIDs is associated with a reduced risk for the development of Alzheimer disease (AD). In this study, 20 commonly used NSAIDs, dapsone, and enantiomers of flurbiprofen were analyzed for their ability to lower the level of the 42-amino-acid form of amyloid β protein (Aβ42) in a human H4 cell line. Thirteen of the NSAIDs and the enantiomers of flurbiprofen were then tested in acute dosing studies in amyloid β protein precursor (APP) transgenic mice, and plasma and brain levels of Aβ and the drug were evaluated. These studies show that (a) eight FDA-approved NSAIDs lower Aβ42 in vivo, (b) the ability of an NSAID to lower Aβ42 levels in cell culture is highly predicative of its in vivo activity, (c) in vivo Aβ42 lowering in mice occurs at drug levels achievable in humans, and (d) there is a significant correlation between Aβ42 lowering and levels of ibuprofen. Importantly, flurbiprofen and its enantiomers selectively lower Aβ42 levels ...
https://taoyantao.com.www.mobile.jci.org/articles/view/18162/figure/4
KEGG DISEASE: Alzheimer diseaseKEGG DISEASE: Alzheimer disease
Alzheimer disease (AD) is a chronic disorder that slowly destroys neurons and causes serious cognitive disability. AD is associated with senile plaques and neurofibrillary tangles (NFTs). Amyloid-beta (Abeta), a major component of senile plaques, has various pathological effects on cell and organelle function. To date genetic studies have revealed four genes that may be linked to autosomal dominant or familial early onset AD (FAD). These four genes include: amyloid precursor protein (APP), presenilin 1 (PS1), presenilin 2 (PS2) and apolipoprotein E (ApoE). All mutations associated with APP and PS proteins can lead to an increase in the production of Abeta peptides, specfically the more amyloidogenic form, Abeta42. It was proposed that Abeta form Ca2+ permeable pores and bind to and modulate multiple synaptic proteins, including NMDAR, mGluR5 and VGCC, leading to the overfilling of neurons with calcium ions. Consequently, cellular Ca2+ disruptions will lead to neuronal apoptosis, autophagy ...
https://www.kegg.jp/entry/H00056
Figures and data in Presynaptic APP levels and synaptic homeostasis are regulated by Akt phosphorylation of huntingtin | eLifeFigures and data in Presynaptic APP levels and synaptic homeostasis are regulated by Akt phosphorylation of huntingtin | eLife
Reducing Akt-mediated huntingtin phosphorylation decreases APP accumulation at the synapse by reducing its anterograde axonal transport and ameliorates learning and memory in a mouse model of familial Alzheimer disease.
https://elifesciences.org/articles/56371/figures
JCI - Autophagy and neurodegenerationJCI - Autophagy and neurodegeneration
Alzheimers disease. Alzheimers disease (AD) is characterized by extracellular amyloid-β (Aβ) plaques, which are generated through amyloid precursor protein (APP) cleavage, and neurofibrillary tangles, comprising paired helical filaments of intracellular, hyperphosphorylated tau, a microtubule-associated protein.. One of the first observations that suggested a role for altered autophagy in AD was the accumulation of autophagic vesicles in affected neurons (9, 10). While initially considered to represent increased autophagy, more recent evidence indicates that this accumulation is due to impaired autophagosome clearance. Presenilin-1 (PS1) is part of the γ-secretase complex required for Aβ production; however, it also functions to facilitate N-glycosylation of the V0a1 subunit of lysosomal vacuolar H+-ATPase (v-ATPase) and its trafficking to the lysosome to enable acidification of this organelle (11). PS1 and PS2 mutations cause familial autosomal-dominant AD (12-14) and result in amyloid ...
https://www.jci.org/articles/view/73944
Amyloid-beta precursor proteinAmyloid-beta precursor protein
"Mutation of the beta-amyloid precursor protein in familial Alzheimer's disease increases beta-protein production". Nature. 360 ... a reproductive regulator that modulates the processing of amyloid-beta precursor protein and amyloid-beta deposition". The ... Amyloid-beta precursor protein is an ancient and highly conserved protein. In humans, the gene APP is located on chromosome 21 ... Amyloid-beta precursor protein (APP) is an integral membrane protein expressed in many tissues and concentrated in the synapses ...
https://en.wikipedia.org/wiki/Amyloid-beta_precursor_protein
Amyloid-beta precursor protein secretaseAmyloid-beta precursor protein secretase
Among other roles in the cell, secretases act on the amyloid-beta precursor protein (APP) to cleave the protein into three ... Sequential cleavage by beta-secretase 1 (BACE) and gamma-secretase (γ-secretase) produces the amyloid-beta peptide fragment ... no amyloid beta is formed because α-secretase recognizes a target protein sequence closer to the cell surface than BACE. The ... BACE is a transmembrane protein with an extracellular aspartic acid protease domain. γ-secretase is actually a protein complex ...
https://en.wikipedia.org/wiki/Amyloid-beta_precursor_protein_secretase
Glyceraldehyde 3-phosphate dehydrogenaseGlyceraldehyde 3-phosphate dehydrogenase
... skeletal muscle-specific Ca2+/calmodulin-dependent protein kinase; Akt; Beta-amyloid precursor protein (betaAPP); Huntingtin. ... For example, GAPDH interactions with beta-amyloid precursor protein (betaAPP) could interfere with its function regarding the ... GAPDH participates in a number of biological functions through its protein-protein interactions with: tubulin to facilitate ... where it ubiquitinates and degrades nuclear proteins during nitrosative stress conditions; GAPDH's competitor of Siah protein ...
https://en.wikipedia.org/wiki/Glyceraldehyde_3-phosphate_dehydrogenase
CTNNBIP1CTNNBIP1
Chen Y, Bodles AM (2007). "Amyloid precursor protein modulates beta-catenin degradation". Journal of Neuroinflammation. 4: 29. ... Beta-catenin-interacting protein 1 is a protein that is encoded in humans by the CTNNBIP1 gene. The protein encoded by this ... Sharma M, Henderson BR (2007). "IQ-domain GTPase-activating protein 1 regulates beta-catenin at membrane ruffles and its role ... 2007). "Large-scale mapping of human protein-protein interactions by mass spectrometry". Mol. Syst. Biol. 3 (1): 89. doi: ...
https://en.wikipedia.org/wiki/CTNNBIP1
APBB1IPAPBB1IP
Amyloid beta A4 precursor protein-binding family B member 1-interacting protein (APBB1IP), also known as APBB1-interacting ... "Entrez Gene: amyloid beta (A4) precursor protein-binding". Inagaki T, Suzuki S, Miyamoto T, Takeda T, Yamashita K, Komatsu A, ... 1997). "The WW domain of neural protein FE65 interacts with proline-rich motifs in Mena, the mammalian homolog of Drosophila ... protein 1 or Rap1-GTP-interacting adapter molecule (RIAM) is a protein that in humans is encoded by the APBB1IP gene. GRCh38: ...
https://en.wikipedia.org/wiki/APBB1IP
Down syndrome researchDown syndrome research
APP is an Amyloid beta A4 precursor protein. It is suspected to have a major role in cognitive difficulties. Another gene, ETS2 ... Online Mendelian Inheritance in Man (OMIM): AMYLOID BETA A4 PRECURSOR PROTEIN; APP - 104760, gene located at 21q21. Retrieved ... Down syndrome individuals to develop Alzheimer's pathology is the gene that encodes the precursor of the amyloid protein. ... Neurofibrillary tangles and amyloid plaques are commonly found in both Down syndrome and Alzheimer's individuals. Layer II of ...
https://en.wikipedia.org/wiki/Down_syndrome_research
APLP2APLP2
... Amyloid beta (A4) precursor-like protein 2". Leach R, Ko M, Krawetz SA (1999). "Assignment of amyloid-precursor-like ... "Association of a novel human FE65-like protein with the cytoplasmic domain of the beta-amyloid precursor protein". Proceedings ... "APLP2 - Amyloid-like protein 2 precursor - Homo sapiens (Human) - APLP2 gene & protein". www.uniprot.org. Retrieved 2016-10-03 ... APLP2 is part of a family of mammalian membrane proteins along with APLP1 and amyloid precursor protein (APP). Since APP plays ...
https://en.wikipedia.org/wiki/APLP2
Estrogen and neurodegenerative diseasesEstrogen and neurodegenerative diseases
1994). "Estrogen regulates metabolism of Alzheimer amyloid beta precursor protein". Journal of Biological Chemistry. 269 (18): ... Amyloid precursor protein (APP) proteolysis is fundamental for production of Aβ peptides implicated in AD pathology. By using a ... Amyloid plaques formed by amyloid-β (Aβ) deposition and neurofibrillary tangles formed by tau protein phosphorylation are ... The role of estrogens is mostly mediated by two nuclear receptors (ER alpha and ER beta) and a membrane-associated G-protein ( ...
https://en.wikipedia.org/wiki/Estrogen_and_neurodegenerative_diseases
Beta-secretase 2Beta-secretase 2
... cleaves at the beta site and within the amyloid-beta region of the amyloid-beta precursor protein". Proceedings of the National ... Amyloid beta peptide is generated by proteolytic cleavage of amyloid precursor protein by 2 proteases, one of which is the ... "Human aspartic protease memapsin 2 cleaves the beta-secretase site of beta-amyloid precursor protein". Proceedings of the ... cleaves the amyloid precursor protein at the beta-secretase site". Molecular and Cellular Neurosciences. 16 (5): 609-19. doi: ...
https://en.wikipedia.org/wiki/Beta-secretase_2
Christine Van BroeckhovenChristine Van Broeckhoven
Amyloid beta protein precursor gene and hereditary cerebral hemorrhage with amyloidosis, Science. 1990 June 1;248(4959):1120-2 ... in 1993 she and three other scientists were awarded the American Potamkin Prize for their work on the amyloid precursor protein ...
https://en.wikipedia.org/wiki/Christine_Van_Broeckhoven
APBB3APBB3
Amyloid beta A4 precursor protein-binding family B member 3 is a protein that in humans is encoded by the APBB3 gene. The ... 2004). "Generation of the beta-amyloid peptide and the amyloid precursor protein C-terminal fragment gamma are potentiated by ... "Entrez Gene: APBB3 amyloid beta (A4) precursor protein-binding, family B, member 3". Tanahashi H, Tabira T (1999). "Molecular ... It is found in the cytoplasm and binds to the intracellular domain of the Alzheimer's disease beta-amyloid precursor protein ( ...
https://en.wikipedia.org/wiki/APBB3
Tm2 domain containing 1Tm2 domain containing 1
Kirfel G, Borm B, Rigort A, Herzog V (2002). "The secretory beta-amyloid precursor protein is a motogen for human epidermal ... This protein may be a target of neurotoxic beta-amyloid peptide, and may mediate cellular vulnerability to beta-amyloid peptide ... The protein encoded by this gene is a beta-amyloid peptide-binding protein. It contains a structural module related to that of ... "Beta-amyloid peptide binding protein does not couple to G protein in a heterologous Xenopus expression system". J. Neurosci. ...
https://en.wikipedia.org/wiki/Tm2_domain_containing_1
APPBP1APPBP1
The protein encoded by this gene binds to the beta-amyloid precursor protein. Beta-amyloid precursor protein is a cell surface ... APPBP1 (Amyloid Precursor Protein-Binding Protein 1) binds to the Amyloid Precursor Protein (APP) carboxy terminal domain. ... APPBP1 amyloid beta precursor protein binding protein 1". Chen Y, McPhie DL, Hirschberg J, Neve RL (March 2000). "The amyloid ... APPBP1 was first cloned and identified by its interaction with the C-terminus of beta-amyloid protein precursor (precursor to ...
https://en.wikipedia.org/wiki/APPBP1
KIAA0825KIAA0825
The other is the Amyloid-beta precursor protein. This protein is an integral membrane protein found most commonly in the ... September 2011). "Interactions of pathological hallmark proteins: tubulin polymerization promoting protein/p25, beta-amyloid, ... Several programs suggest that the secondary structure of the protein is mainly helices with only a few beta sheets. Analysis of ... The subcellular localization for the protein is predicted to be the nucleus and the cytoplasm. This suggests that the protein ...
https://en.wikipedia.org/wiki/KIAA0825
ReelinReelin
"Reelin in plaques of beta-amyloid precursor protein and presenilin-1 double-transgenic mice". Neuroscience Letters. 316 (3): ... "Interaction of cytosolic adaptor proteins with neuronal apolipoprotein E receptors and the amyloid precursor protein". The ... Reelin has been shown to interact with amyloid precursor protein, and, according to one in-vitro study, is able to counteract ... "Interaction of reelin with amyloid precursor protein promotes neurite outgrowth". The Journal of Neuroscience. 29 (23): 7459-73 ...
https://en.wikipedia.org/wiki/Reelin
SHC3SHC3
"Tyrosine phosphorylation of the beta-amyloid precursor protein cytoplasmic tail promotes interaction with Shc". The Journal of ... SHC-transforming protein 3 is a protein that in humans is encoded by the SHC3 gene. SHC3 has been shown to interact with RICS ... Nakamura T, Komiya M, Sone K, Hirose E, Gotoh N, Morii H, Ohta Y, Mori N (December 2002). "Grit, a GTPase-activating protein ... O'Bryan JP, Songyang Z, Cantley L, Der CJ, Pawson T (April 1996). "A mammalian adaptor protein with conserved Src homology 2 ...
https://en.wikipedia.org/wiki/SHC3
ParvulinParvulin
2006). The prolyl isomerase Pin1 regulates amyloid precursor protein processing and amyloid-beta production. Nature 440(7083): ... Absence of Pin1 activity in humans has also been implicated in the folding and processing of the amyloid precursor protein, ... Parvulin, a 92-amino acid protein discovered in E. coli in 1994, is the smallest known protein with prolyl isomerase activity, ... 2000). Proline isomerizarion and its catalysis in protein folding. In Mechanisms of Protein Folding 2nd ed. Ed. RH Pain. ...
https://en.wikipedia.org/wiki/Parvulin
CLSTN1CLSTN1
... enhance the X11-like protein-mediated stabilization of amyloid beta-protein precursor metabolism". The Journal of Biological ... enhance the X11-like protein-mediated stabilization of amyloid beta-protein precursor metabolism". The Journal of Biological ... "Coordinated metabolism of Alcadein and amyloid beta-protein precursor regulates FE65-dependent gene transactivation". The ... "Coordinated metabolism of Alcadein and amyloid beta-protein precursor regulates FE65-dependent gene transactivation". The ...
https://en.wikipedia.org/wiki/CLSTN1
Beta-secretase 1Beta-secretase 1
... , also known as beta-site amyloid precursor protein cleaving enzyme 1, beta-site APP cleaving enzyme 1 (BACE1 ... "Beta-secretase cleavage of Alzheimer's amyloid precursor protein by the transmembrane aspartic protease BACE". Science. 286 ( ... "Expression and activity of beta-site amyloid precursor protein cleaving enzyme in Alzheimer's disease". Biochemical Society ... Drugs to block this enzyme (BACE inhibitors) in theory would prevent the buildup of beta-amyloid and (per the Amyloid ...
https://en.wikipedia.org/wiki/Beta-secretase_1
APBB2APBB2
The protein encoded by this gene interacts with the cytoplasmic domains of amyloid beta (A4) precursor protein and amyloid beta ... Amyloid beta A4 precursor protein-binding family B member 2 is a protein that in humans is encoded by the APBB2 gene. ... 2004). "Generation of the beta-amyloid peptide and the amyloid precursor protein C-terminal fragment gamma are potentiated by ... "Association of a novel human FE65-like protein with the cytoplasmic domain of the beta-amyloid precursor protein". Proc. Natl. ...
https://en.wikipedia.org/wiki/APBB2
UBB+1UBB+1
"Frameshift mutants of beta amyloid precursor protein and ubiquitin-B in Alzheimer's and Down patients". Science. 279 (5348): ... Dennissen FJ, Kholod N, Steinbusch HW, Van Leeuwen FW (2010). "Misframed proteins and neurodegeneration: a novel view on ...
https://en.wikipedia.org/wiki/UBB 1
NECAB3NECAB3
The protein encoded by this gene interacts with the amino-terminal domain of the amyloid beta A4 precursor protein-binding ... "Entrez Gene: APBA2BP amyloid beta (A4) precursor protein-binding, family A, member 2 binding protein". Human NECAB3 genome ... may play an important role in the regulatory system of amyloid precursor protein metabolism and beta-amyloid generation. This ... "Regulation of X11L-dependent amyloid precursor protein metabolism by XB51, a novel X11L-binding protein". J Biol Chem. 275 (30 ...
https://en.wikipedia.org/wiki/NECAB3
Joseph BuxbaumJoseph Buxbaum
"Processing of Alzheimer beta/A4 amyloid precursor protein: modulation by agents that regulate protein phosphorylation". ... factor alpha converting enzyme is involved in regulated alpha-secretase cleavage of the Alzheimer amyloid protein precursor". ... "Correlation between elevated levels of amyloid beta-peptide in the brain and cognitive decline". JAMA. 283 (12): 1571-1577. doi ... In Alzheimer disease, Buxbaum has conducted several cell-biological and patient-based analyses of APP and A-beta and he and his ...
https://en.wikipedia.org/wiki/Joseph_Buxbaum
APBB1APBB1
"Regulation of beta-amyloid secretion by FE65, an amyloid protein precursor-binding protein". J. Biol. Chem. 274 (12): 7952-7. ... Amyloid beta A4 precursor protein-binding family B member 1 is a protein that in humans is encoded by the APBB1 gene. The ... "Association of a novel human FE65-like protein with the cytoplasmic domain of the beta-amyloid precursor protein". Proceedings ... "Fe65 and the protein network centered around the cytosolic domain of the Alzheimer's beta-amyloid precursor protein". FEBS Lett ...
https://en.wikipedia.org/wiki/APBB1
Carboxypeptidase B2Carboxypeptidase B2
Matsumoto A, Itoh K, Matsumoto R (2000). "A novel carboxypeptidase B that processes native beta-amyloid precursor protein is ... Mosnier LO, Meijers JC, Bouma BN (2002). "The role of protein S in the activation of thrombin activatable fibrinolysis ... Mosnier LO, Elisen MG, Bouma BN, Meijers JC (2002). "Protein C inhibitor regulates the thrombin-thrombomodulin complex in the ... After thrombin activation, the mature protein downregulates fibrinolysis. Polymorphisms have been described for this gene and ...
https://en.wikipedia.org/wiki/Carboxypeptidase_B2
Cytochrome c oxidaseCytochrome c oxidase
"Regional brain cytochrome oxidase activity in beta-amyloid precursor protein transgenic mice with the Swedish mutation". ... The complex is a large integral membrane protein composed of several metal prosthetic sites and 14 protein subunits in mammals ... Aledo JC, Valverde H, Ruíz-Camacho M, Morilla I, López FD (October 2014). "Protein-protein interfaces from cytochrome c oxidase ... Soltys BJ, Gupta RS (1999). "Mitochondrial proteins at unexpected cellular locations: export of proteins from mitochondria from ...
https://en.wikipedia.org/wiki/Cytochrome_c_oxidase
FBLN1FBLN1
Ohsawa I, Takamura C, Kohsaka S (Mar 2001). "Fibulin-1 binds the amino-terminal head of beta-amyloid precursor protein and ... FBLN1 has been shown to interact with: NOV/CCN3, amyloid precursor protein, entactin, fibrinogen, and fibronectin. ... a novel protein that interacts with the fibronectin receptor beta subunit cytoplasmic domain". Cell. 58 (4): 623-9. doi:10.1016 ... Pan TC, Kluge M, Zhang RZ, Mayer U, Timpl R, Chu ML (Aug 1993). "Sequence of extracellular mouse protein BM-90/fibulin and its ...
https://en.wikipedia.org/wiki/FBLN1
Michael MullanMichael Mullan
"Early-onset Alzheimer's disease caused by mutations at codon 717 of the beta-amyloid precursor protein gene". Nature. 353 (6347 ... Subsequently, he was a co-inventor on the original patents that covered three mutations in the amyloid precursor protein (APP) ... "Amyloid precursor protein in alzheimer's disease", published 1998-08-18 Goate A, Chartier-Harlin MC, Mullan M, Brown J, ... "Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer's disease". Nature. 349 (6311 ...
https://en.wikipedia.org/wiki/Michael_Mullan
CathepsinCathepsin
... B may function as a beta-secretase 1, cleaving amyloid precursor protein to produce amyloid beta. Overexpression of ... After protein concentration is determined, equal amounts of tissue protein are loaded into a gel. The protein is then allowed ... Deficiencies in this protein are linked to multiple forms of galactosialidosis. The cathepsin A activity in lysates of ... Hook, Gregory; Hook, Vivian; Kindy, Mark (2011-01-01). "The cysteine protease inhibitor, E64d, reduces brain amyloid-β and ...
https://en.wikipedia.org/wiki/Cathepsin
CTCFCTCF
"The zinc finger protein CTCF binds to the APBbeta domain of the amyloid beta-protein precursor promoter. Evidence for a role in ... This protein was found to be binding to three regularly spaced repeats of the core sequence CCCTC and thus was named CCCTC ... This model has been demonstrated by the previous work on the beta-globin locus. The binding of CTCF has been shown to have many ... This is in line with the concept that a subpopulation of CTCF associates with the RNA polymerase II (Pol II) protein complex to ...
https://en.wikipedia.org/wiki/CTCF
LECT2LECT2
The secreted protein consists of 133`amino acids (mouse Lect2 consists of two varieties a typical 151 amino acid protein and an ... It has been found repeatedly that the mere presence of LECT2 amyloid tissue deposits does not necessarily indicate the presence ... 2004). "Identification of the leukocyte cell-derived chemotaxin 2 as a direct target gene of beta-catenin in the liver". ... elevated in individuals not only with diagnosed metabolic syndrome but also with a characteristic of and possible precursor to ...
https://en.wikipedia.org/wiki/LECT2
Cerebral amyloid angiopathyCerebral amyloid angiopathy
Mutations in the amyloid precursor protein (APP), Presenilin (PS) 1 and PS2 genes can result in increased rates of cleavage of ... Cerebral amyloid angiopathy (CAA) is a form of angiopathy in which amyloid beta peptide deposits in the walls of small to ... The condition is usually associated with amyloid beta. However, there are types involving other amyloid peptides: the " ... In all cases, it is defined by the deposition of amyloid beta (Aβ) in the leptomeningal and cerebral vessel walls. CAA ...
https://en.wikipedia.org/wiki/Cerebral_amyloid_angiopathy
MeldoniumMeldonium
... meldonium increased cognition and mental performance by reducing amyloid beta deposition in the hippocampus. The mechanism of ... γ-Butyrobetaine is a precursor in the biosynthesis of carnitine.[better source needed] Meldonium is a white crystalline powder ... This complex is then transported through the inner mitochondrial membrane via a transporter protein called carnitine- ... In the mitochondria themselves, meldonium also competitively inhibits the carnitine shuttle protein SLC22A5. This results in ...
https://en.wikipedia.org/wiki/Meldonium
Index of biochemistry articlesIndex of biochemistry articles
... protein isoform - protein nuclear magnetic resonance spectroscopy - protein P16 - protein P34cdc2 - protein precursor - protein ... beta-2 microglobulin - beta adrenergic receptor - beta sheet - beta-1 adrenergic receptor - beta-2 adrenergic receptor - beta- ... amyloid - anabolism - anaerobic respiration - analytical chemistry - androgen receptor - angiotensin - angiotensin II - ... protein - protein biosynthesis - Protein Data Bank - protein design - protein expression - protein folding - ...
https://en.wikipedia.org/wiki/Index_of_biochemistry_articles
MAP3K7IP2MAP3K7IP2
... of N-CoR corepressor and Tip60 coactivator complexes links gene expression by NF-kappaB and beta-amyloid precursor protein". ... of N-CoR corepressor and Tip60 coactivator complexes links gene expression by NF-kappaB and beta-amyloid precursor protein". ... Mitogen-activated protein kinase kinase kinase 7-interacting protein 2 is an enzyme that in humans is encoded by the MAP3K7IP2 ... "Entrez Gene: MAP3K7IP2 mitogen-activated protein kinase kinase kinase 7 interacting protein 2". Thienpont B, Zhang L, Postma AV ...
https://en.wikipedia.org/wiki/MAP3K7IP2
APBA2APBA2
Amyloid beta A4 precursor protein-binding family A member 2 is a protein that in humans is encoded by the APBA2 gene. This ... enhance the X11-like protein-mediated stabilization of amyloid beta-protein precursor metabolism". J. Biol. Chem. 278 (49): ... "Entrez Gene: APBA2 amyloid beta (A4) precursor protein-binding, family A, member 2 (X11-like)". Araki Y, Tomita S, Yamaguchi H ... Borg JP, Yang Y, De Taddéo-Borg M, Margolis B, Turner RS (1998). "The X11alpha protein slows cellular amyloid precursor protein ...
https://en.wikipedia.org/wiki/APBA2
SNX8SNX8
The amyloid precursor protein (APP) is consecutively transported from the ER after its synthesis to the plasma membrane via the ... "Beta-amyloid toxicity modifier genes and the risk of Alzheimer's disease". American Journal of Neurodegenerative Disease. 1 (2 ... are involved in protein-protein interactions. The SNX8 protein, even though is very similar to the other sorting nexins, ... SNX8 protein regulates cholesterol levels as an activator of the SREBPs (Sterol Regulatory Element Binding Proteins), which is ...
https://en.wikipedia.org/wiki/SNX8
Estrogen receptor betaEstrogen receptor beta
Thus, ERβ helps control Aβ levels by maintaining the protein it is derived from, β-amyloid precursor protein. ERβ helps by up- ... The pathology of AD is also associated with accumulation of amyloid beta peptide (Aβ). While a proper concentration of Aβ in ... Brandenberger AW, Tee MK, Jaffe RB (March 1998). "Estrogen receptor alpha (ER-alpha) and beta (ER-beta) mRNAs in normal ovary, ... February 1998). "The complete primary structure of human estrogen receptor beta (hER beta) and its heterodimerization with ER ...
https://en.wikipedia.org/wiki/Estrogen_receptor_beta
UbiquitinUbiquitin
Higher levels of ubiquilin in the brain have been shown to decrease malformation of amyloid precursor protein (APP), which ... This compact globular beta-grasp fold is found in ubiquitin, UBLs, and proteins that comprise a ubiquitin-like domain, e.g. the ... coordinating the cellular localization of proteins, activating and inactivating proteins, and modulating protein-protein ... "Ubiquilin-1 is a molecular chaperone for the amyloid precursor protein". The Journal of Biological Chemistry. 286 (41): 35689- ...
https://en.wikipedia.org/wiki/Ubiquitin
Interleukin 1-alphaInterleukin 1-alpha
Both the 31kDa precursor form of IL-1α and its 18kDa mature form are biologically active. The 31 kDa IL-1α precursor is ... IL1A+protein,+human at the US National Library of Medicine Medical Subject Headings (MeSH) This article incorporates text from ... The three-dimensional structure of the IL-1α contains an open-ended barrel composed entirely of beta-pleated strands. Crystal ... serum amyloid A inducer or hepatocyte-stimulating factor (HSP), catabolin, hemopoetin-1 (H-1), endogenous pyrogen (EP), and ...
https://en.wikipedia.org/wiki/Interleukin_1-alpha
C99 (disambiguation)C99 (disambiguation)
... a fragment of the amyloid precursor protein created by beta-secretase C99Shell, also known as C99, is a malicious web shell C99 ...
https://en.wikipedia.org/wiki/C99_(disambiguation)
GAB2GAB2
... in playing a role in the pathogenesis of Alzheimer's disease via its interaction with tau and amyloid precursor proteins. GAB2 ... Yu WM, Hawley TS, Hawley RG, Qu CK (April 2002). "Role of the docking protein Gab2 in beta(1)-integrin signaling pathway- ... GRB2-associated-binding protein 2 also known as GAB2 is a protein that in humans is encoded by the GAB2 gene. GAB2 is a docking ... GAB proteins were one of the first docking proteins identified in the mammalian signal transduction pathway. GAB2 along with ...
https://en.wikipedia.org/wiki/GAB2
Laminin subunit alpha-1Laminin subunit alpha-1
Cáceres J, Brandan E (1997). "Interaction between Alzheimer's disease beta A4 precursor protein (APP) and the extracellular ... Zahedi K (1997). "Characterization of the binding of serum amyloid P to laminin". J. Biol. Chem. 272 (4): 2143-8. doi:10.1074/ ... "HIV-protein-mediated alterations in T cell interactions with the extracellular matrix proteins and endothelium". Arch. Immunol ... Laminin subunit alpha-1 is a protein that in humans is encoded by the LAMA1 gene. Laminin, alpha 1 has been shown to interact ...
https://en.wikipedia.org/wiki/Laminin_subunit_alpha-1
Low-density lipoprotein receptor-related protein 8Low-density lipoprotein receptor-related protein 8
... such as amyloid precursor protein, to ApoER2. This protein aids in a cell's migrational functions. Knockout studies of FE65 ... The presence of amyloid beta (Aβ) protein deposits in neuronal extracellular space is one of the hallmarks of Alzheimer's ... of a decrease in expression of LRP8 is when gamma secretase cleaves LRP8 as well as the ligand amyloid precursor protein (APP ... New evidence suggests ApoER2 plays a major role in the regulation of amyloid-β formation in the brain. The amyloid-β peptide is ...
https://en.wikipedia.org/wiki/Low-density_lipoprotein_receptor-related_protein_8
Epigenetics of neurodegenerative diseasesEpigenetics of neurodegenerative diseases
BACE1 is an enzymatic protein that cleaves the Amyloid Precursor Protein into the insoluble amyloid beta form, which then ... and by amyloid-beta senile plaques amyloid-beta senile plaques. Several genetic factors have been identified as contributing to ... combined with the observed increase in AD brains of BACE1-AS and corresponding increases in BACE1 protein and amyloid beta, ... including mutations to the amyloid precursor protein (APP) and presenilins 1 and 2 genes, and familial inheritance of ...
https://en.wikipedia.org/wiki/Epigenetics_of_neurodegenerative_diseases
Lydia Villa-KomaroffLydia Villa-Komaroff
This paper provided the first direct evidence that a fragment of the amyloid precursor protein could kill neurons, and helped ... Before this publication, it was unclear whether amyloid beta was a byproduct of neuronal degeneration or a contributor to that ... amyloid beta) causes degeneration of brain cells (neurons), work done in conjunction with a postdoctoral fellow in her ... "Neurotoxicity of a fragment of the amyloid precursor associated with Alzheimer's disease". Science. 245 (4916): 417-420. ...
https://en.wikipedia.org/wiki/Lydia_Villa-Komaroff
HSD17B10HSD17B10
... has been shown to interact with Amyloid precursor protein. GRCh38: Ensembl release 89: ENSG00000072506 - Ensembl, May ... "An intracellular protein that binds amyloid-beta peptide and mediates neurotoxicity in Alzheimer's disease". Nature. 389 (6652 ... "A human brain L-3-hydroxyacyl-coenzyme A dehydrogenase is identical to an amyloid beta-peptide-binding protein involved in ... "A human brain L-3-hydroxyacyl-coenzyme A dehydrogenase is identical to an amyloid beta-peptide-binding protein involved in ...
https://en.wikipedia.org/wiki/HSD17B10
Granulocyte colony-stimulating factorGranulocyte colony-stimulating factor
G-CSF has been shown to reduce inflammation, reduce amyloid beta burden, and reverse cognitive impairment in a mouse model of ... and Ras/mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signal ... White blood cells The G-CSF-receptor is present on precursor cells in the bone marrow, and, in response to stimulation by G-CSF ... The natural human glycoprotein exists in two forms, a 174- and 177-amino-acid-long protein of molecular weight 19,600 grams per ...
https://en.wikipedia.org/wiki/Granulocyte_colony-stimulating_factor
ACTC1ACTC1
Alzheimer amyloid precursor protein and pro-interleukin 1 beta as substrates of the protease from human immunodeficiency virus ... Shuster CB, Lin AY, Nayak R, Herman IM (1997). "Beta cap73: a novel beta actin-specific binding protein". Cell Motility and the ... Cardiac alpha actin is a 42.0 kDa protein composed of 377 amino acids. Cardiac alpha actin is a filamentous protein extending ... ". "Protein Information - Basic Information: Protein COPaKB ID: P68032". Cardiac Organellar Protein Atlas Knowledgebase. ...
https://en.wikipedia.org/wiki/ACTC1
LeptinLeptin
"LEP - Leptin precursor - Homo sapiens (Human) - LEP gene & protein". www.uniprot.org. Retrieved 8 May 2022. Mantzoros CS (April ... Greco SJ, Sarkar S, Johnston JM, Tezapsidis N (February 2009). "Leptin regulates tau phosphorylation and amyloid through AMPK ... activator of beta islet cells, and growth factor. In vertebrates, the nervous system consists of two main parts, the central ... Human leptin is a 16-kDa protein of 167 amino acids. A human mutant leptin was first described in 1997, and subsequently six ...
https://en.wikipedia.org/wiki/Leptin
PresenilinPresenilin
An important part of the disease process in Alzheimer's disease is the accumulation of Amyloid beta (Aβ) protein. To form Aβ, ... The best-characterized gamma-secretase substrates are the Notch receptor and amyloid precursor protein (APP). Presenilins' role ... January 1997). "Mutant presenilins of Alzheimer's disease increase production of 42-residue amyloid beta-protein in both ... or the amyloid precursor protein (APP) can be found. The majority of these cases carry mutant presenilin genes. ...
https://en.wikipedia.org/wiki/Presenilin
1,2,3,4,6-Pentagalloyl glucose1,2,3,4,6-Pentagalloyl glucose
6-penta-O-galloyl-beta-D-glucopyranose have potent anti-aggregation effects on Alzheimer's amyloid beta proteins in vitro and ... It is a gallotannin and the precursor of ellagitannins. Pentagalloyl glucose can precipitate proteins, including human salivary ... Chen Y, Hagerman AE (February 2005). "Reaction pH and protein affect the oxidation products of beta-pentagalloyl glucose". Free ... The enzyme beta-glucogallin-tetrakisgalloylglucose O-galloyltransferase uses 1-O-galloyl-beta-D-glucose and 1,2,3,6-tetrakis-O- ...
https://en.wikipedia.org/wiki/1,2,3,4,6-Pentagalloyl_glucose
Alternative abiogenesis scenariosAlternative abiogenesis scenarios
Primordial genetics: Information transfer in a pre-RNA world based on self-replicating beta-sheet amyloid conformers". Journal ... protein and lipid precursors in a cyanosulfidic protometabolism". Nature Chemistry. 7 (4): 301-307. Bibcode:2015NatCh...7..301P ... Maury, C. P. (2009). "Self-proagating beta-sheet polypeptide structures as prebiotic informational entities:The amyloid world ... The product molecule joins the precursor molecules, which in turn produce more product molecules from more precursor molecules ...
https://en.wikipedia.org/wiki/Alternative_abiogenesis_scenarios
MAPK8IP1MAPK8IP1
... binds the cytoplasmic domain of the Alzheimer's beta-amyloid precursor protein (APP)". J. Biol. Chem. 277 (5): 3767-75. doi: ... 2001). "c-Jun N-terminal kinase (JNK)-interacting protein-1b/islet-brain-1 scaffolds Alzheimer's amyloid precursor protein with ... and decrease IL-1 beta and MAP kinase kinase 1 (MEKK1) induced apoptosis in pancreatic beta cells. This protein also functions ... The protein encoded by this gene is a regulator of the pancreatic beta-cell function. It is highly similar to JIP-1, a mouse ...
https://en.wikipedia.org/wiki/MAPK8IP1
Actin, cytoplasmic 2Actin, cytoplasmic 2
Alzheimer amyloid precursor protein and pro-interleukin 1 beta as substrates of the protease from human immunodeficiency virus ... "Thymosin beta 10 and thymosin beta 4 are both actin monomer sequestering proteins". The Journal of Biological Chemistry. 268 (1 ... A Thr278Ile mutation was identified in helix 9 of gamma-actin protein, which is predicted to alter protein structure. This ... Pedrotti B, Colombo R, Islam K (1995). "Microtubule associated protein MAP1A is an actin-binding and crosslinking protein". ...
https://en.wikipedia.org/wiki/Actin,_cytoplasmic_2
Dock3Dock3
Chen Q, Kimura H, Schubert D (2002). "A novel mechanism for the regulation of amyloid precursor protein metabolism". J. Cell ... a transmembrane enzyme involved in the generation of beta amyloid (Aβ), accumulation of which is an important step in the ... Dock3 specifically activates the small G protein Rac. Dock3 was originally discovered in a screen for proteins that bind ... Dock3 is part of a large class of proteins (GEFs) which contribute to cellular signalling events by activating small G proteins ...
https://en.wikipedia.org/wiki/Dock3
UBE1CUBE1C
The encoded enzyme associates with AppBp1, an amyloid beta precursor protein binding protein, to form a heterodimer, and then ... Chen, Y; McPhie D L; Hirschberg J; Neve R L (March 2000). "The amyloid precursor protein-binding protein APP-BP1 drives the ... Chen Y, McPhie DL, Hirschberg J, Neve RL (2000). "The amyloid precursor protein-binding protein APP-BP1 drives the cell cycle ... The modification of proteins with ubiquitin is an important cellular mechanism for targeting abnormal or short-lived proteins ...
https://en.wikipedia.org/wiki/UBE1C
Carole LaBonneCarole LaBonne
"Overexpression of amyloid precursor protein A4 (beta-amyloid) immunoreactivity in genetically transformed cells: implications ... In subsequent work she demonstrated that Snail-family proteins are required for both establishing the neural crest stem cell ...
https://en.wikipedia.org/wiki/Carole_LaBonne
Apba2 MGI Mouse Gene Detail - MGI:1261791 - amyloid beta (A4) precursor protein-binding, family A, member 2Apba2 MGI Mouse Gene Detail - MGI:1261791 - amyloid beta (A4) precursor protein-binding, family A, member 2
PR:000004116 amyloid-beta A4 precursor protein-binding family A member 2 ... protein coding gene. Chr7:64151308-64403626 (+). 129S1/SvImJ MGP_129S1SvImJ_G0032339. protein coding gene. Chr7:65646611- ... protein coding gene. Chr7:67286145-67518754 (+). CAST/EiJ MGP_CASTEiJ_G0031372. protein coding gene. Chr7:57046864-57311838 (+) ... protein coding gene. Chr7:66384452-66629392 (+). C57BL/6NJ MGP_C57BL6NJ_G0032823. protein coding gene. Chr7:68490268-68768190 ...
http://www.informatics.jax.org/marker/MGI:1261791
Human Amyloid beta (A4) Precursor Protein (APP) Protein (Myc-DYKDDDDK Tag), Recombinant | ABIN2714676Human Amyloid beta (A4) Precursor Protein (APP) Protein (Myc-DYKDDDDK Tag), Recombinant | ABIN2714676
Precursor Protein (APP) Protein (Myc-DYKDDDDK Tag). Spezies: Human. Quelle: HEK-293 Cells. Jetzt Produkt ABIN2714676 bestellen. ... amyloid beta (A4) precursor protein, beta amyloid protein precursor-like, amyloid beta (A4) precursor protein a, amyloid beta ... APP (Amyloid beta (A4) Precursor Protein (APP)) Andere Bezeichnung Amyloid beta a4 Protein,app (APP Produkte) Synonyme AAA, ... APP (Amyloid beta (A4) Precursor Protein (APP)) Protein-Typ Recombinant Proteineigenschaft Transcript Variant 2 Spezies Alle ...
https://www.antikoerper-online.de/protein/2714676/Amyloid+beta+A4+Precursor+Protein+APP+Transcript+Variant+2+protein+Myc-DYKDDDDK+Tag/
Glycogen synthase kinase-3 signaling in Alzheimers disease : regulation of beta-amyloid precursor protein processing and...Glycogen synthase kinase-3 signaling in Alzheimer's disease : regulation of beta-amyloid precursor protein processing and...
... regulation of beta-amyloid precursor protein processing and amyloid beta protein production Ly, Philip T.T. Abstract. Glycogen ... regulation of beta-amyloid precursor protein processing and amyloid beta protein production ... The Aβ peptide is generated through sequential cleavages of the β-amyloid precursor protein by β-secretase (BACE1) and γ- ... The Aβ peptide is generated through sequential cleavages of the β-amyloid precursor protein by β-secretase (BACE1) and γ- ...
https://open.library.ubc.ca/soa/cIRcle/collections/ubctheses/24/items/1.0072944
The orphan drug dichloroacetate reduces amyloid beta-peptide production whilst promoting non-amyloidogenic proteolysis of the...The orphan drug dichloroacetate reduces amyloid beta-peptide production whilst promoting non-amyloidogenic proteolysis of the...
... reduces amyloid beta-peptide production whilst promoting non-amyloidogenic proteolysis of the amyloid precursor protein. PLoS ... whilst inhibiting β-secretase processing of endogenous amyloid precursor protein and the subsequent generation of amyloid beta- ... amyloid beta-peptide formation and has the additional benefit of generating a neuroprotective soluble amyloid precursor protein ... reduces amyloid beta-peptide production whilst promoting non-amyloidogenic proteolysis of the amyloid precursor protein ...
https://eprints.lancs.ac.uk/id/eprint/164650/
Presenilin-dependent gamma-secretase processing of beta-amyloid precursor protein at a site corresponding to the S3 cleavage of...Presenilin-dependent gamma-secretase processing of beta-amyloid precursor protein at a site corresponding to the S3 cleavage of...
The similar gamma-secretase cleavage of the beta-amyloid precursor protein (betaAPP) results in the secretion of amyloid beta- ... The similar gamma-secretase cleavage of the beta-amyloid precursor protein (betaAPP) results in the secretion of amyloid beta- ... Presenilin-dependent gamma-secretase processing of beta-amyloid precursor protein at a site corresponding to the S3 cleavage of ...
https://escholarship.org/uc/item/8gt6h06k
RCSB PDB - 2FK3: Structure of the Alzheimers Amyloid Precursor Protein (APP) Copper Binding Domain in large unit cell formRCSB PDB - 2FK3: Structure of the Alzheimer's Amyloid Precursor Protein (APP) Copper Binding Domain in 'large unit cell' form
Structure of the Alzheimers Amyloid Precursor Protein (APP) Copper Binding Domain in large unit cell form ... Amyloid beta peptide (Abeta), generated by proteolytic cleavage of the amyloid precursor protein (APP), is central to AD ... Amyloid beta peptide (Abeta), generated by proteolytic cleavage of the amyloid precursor protein (APP), is central to AD ... Amyloid beta A4 protein precursor. A, B, C, D, E, F, G, H ... Structure of the Alzheimers Amyloid Precursor Protein (APP) ...
https://www.rcsb.org/structure/2FK3
Screening exons 16 and 17 of the amyloid precursor protein gene in sporadic early-onset Alzheimers diseaseScreening exons 16 and 17 of the amyloid precursor protein gene in sporadic early-onset Alzheimer's disease
A total of 451 sEOAD samples were screened for known causative mutations in exons 16 and 17 of the amyloid precursor protein ( ... Amyloid beta-Protein Precursor Grant support * Z01 AG000950-06/Intramural NIH HHS/United States ... Screening exons 16 and 17 of the amyloid precursor protein gene in sporadic early-onset Alzheimers disease Neurobiol Aging. ... A total of 451 sEOAD samples were screened for known causative mutations in exons 16 and 17 of the amyloid precursor protein ( ...
https://pubmed.ncbi.nlm.nih.gov/26803359/
MedlinePlus: GenesMedlinePlus: Genes
APP: amyloid beta precursor protein. *APRT: adenine phosphoribosyltransferase. *APTX: aprataxin. *AQP2: aquaporin 2 ...
https://medlineplus.gov/genetics/gene
Alzheimers Disease and Sleep DisruptionAlzheimer's Disease and Sleep Disruption
The proteolytic processing of the precursor protein beta-amyloid. Image Credit: Ilusmedical / Shutterstock ... can significantly increase levels of beta-amyloid in the brain - one of the main toxic proteins that are linked to Alzheimers ... However, studies have shown a marked increase in beta-amyloid levels in the brains of patients with OSA compared to those who ... Lack of Sleep and Beta-Amyloid. Recent studies have shown that lack of sleep, for even one night, ...
https://www.news-medical.net/health/Alzheimers-Disease-and-Sleep-Disruption.aspx
Alcadein cleavages by amyloid β-precursor protein (APP) α- and γ-secretases generate small peptides, p3-Alcs, indicating...
Amyloid Precursor Protein Secretases Medicine & Life Sciences 66% * Amyloid beta-Protein Precursor Medicine & Life Sciences 62% ... Alcadein cleavages by amyloid β-precursor protein (APP) α- and γ-secretases generate small peptides, p3-Alcs, indicating ... Alcadein cleavages by amyloid β-precursor protein (APP) α- and γ-secretases generate small peptides, p3-Alcs, indicating ... Alcadein cleavages by amyloid β-precursor protein (APP) α- and γ-secretases generate small peptides, p3-Alcs, indicating ...
https://jhu.pure.elsevier.com/en/publications/alcadein-cleavages-by-amyloid-%CE%B2-precursor-protein-app-%CE%B1-and-%CE%B3-sec-5
Search Ageing-Associated Genes in HumansSearch Ageing-Associated Genes in Humans
amyloid beta (A4) precursor protein. APP. 95. APTX. aprataxin. APTX. 110. AR. androgen receptor. AR. ... platelet-derived growth factor receptor, beta polypeptide. PDGFRB. 87. PDPK1. 3-phosphoinositide dependent protein kinase 1. ... protein tyrosine phosphatase, non-receptor type 1. PTPN1. 19. PTPN11. protein tyrosine phosphatase, non-receptor type 11. ... protein phosphatase, Mg2+/Mn2+ dependent, 1D. PPM1D. 227. PPP1CA. protein phosphatase 1, catalytic subunit, alpha isozyme. ...
https://genomics.senescence.info/genes/query.php?show=4&sort=2
MMRRC:034839-JAXMMRRC:034839-JAX
Hemizygous: These R1.40 transgenic mice express all mRNA and protein isoforms of the human amyloid beta (A4) precursor protein ... A 650 kb YAC transgene containing the entire human amyloid beta (A4) precursor protein (APP) gene, and approximately 250 kb of ... Altered metabolism of familial Alzheimers disease-linked amyloid precursor protein variants in yeast artificial chromosome ... Brain and plasma levels of amyloid beta-40 and -42 are variable as well (B6-R1.40 > 129S1-R1.40 > D2-R1.40). In addition, the ...
https://www.mmrrc.org/catalog/sds.php?mmrrc_id=34839
A Diet Enriched with the Omega-3 Fatty Acid Docosahexaenoic Acid Reduces Amyloid Burden in an Aged Alzheimer Mouse Model |...A Diet Enriched with the Omega-3 Fatty Acid Docosahexaenoic Acid Reduces Amyloid Burden in an Aged Alzheimer Mouse Model |...
Sisodia SS (1992) Beta-amyloid precursor protein cleavage by a membrane-bound protease. Proc Natl Acad Sci USA 89: 6075-6079. ... Constitutive alpha-secretase cleavage of the beta-amyloid precursor protein in the furin-deficient LoVo cell line: involvement ... transgenic mouse model to evaluate the impact of dietary DHA on amyloid precursor protein (APP) processing and amyloid burden. ... Therefore, the purpose of this study was to evaluate the impact of DHA on Aβ production and amyloid precursor protein (APP) ...
https://www.jneurosci.org/node/363077.full.print
Study on the Mechanisms and Experimental Verification of Cuscuta-Salvia (Tusizi-Danshen) in the Treatment of Polycystic Ovary...Study on the Mechanisms and Experimental Verification of Cuscuta-Salvia (Tusizi-Danshen) in the Treatment of Polycystic Ovary...
Amyloid-beta precursor protein. 186. ESR1. Estrogen receptor. 187. DRD2. D (2) dopamine receptor ... 2.5 Establishment of protein-protein interaction (PPI) network. To interpret the interaction between target proteins, the ... Second, a protein-protein interaction (PPI) network was established. Core genes were selected using Cytoscape software plugin. ... Protein interactions with a confidence score , 0.4 were analyzed (Wang et al. 2020). Next, the nodes and score information were ...
https://www.researchsquare.com/article/rs-642886/v1
Curcumin and cognition: a randomised, placebo-controlled, double-blind study of community-dwelling older adults | British...Curcumin and cognition: a randomised, placebo-controlled, double-blind study of community-dwelling older adults | British...
2010) Curcumin decreases amyloid-beta peptide levels by attenuating the maturation of amyloid-beta precursor protein. J Biol ... 2005) Curcumin inhibits formation of amyloid beta oligomers and fibrils, binds plaques, and reduces amyloid in vivo . J Biol ... 1985) Amyloid plaque core protein in Alzheimer disease and down syndrome. Proc Natl Acad Sci U S A 82, 4245-4249.CrossRefGoogle ... In addition to these properties, both in vitro and in vivo studies have shown that curcumin can bind to the proteins β amyloid ...
https://www.cambridge.org/core/journals/british-journal-of-nutrition/article/curcumin-and-cognition-a-randomised-placebocontrolled-doubleblind-study-of-communitydwelling-older-adults/83419D0C8B37ACD8BBC7C27B91FBAF58
Neurodegenerative Diseases | The New York Academy of SciencesNeurodegenerative Diseases | The New York Academy of Sciences
A high-throughput screen to identify inhibitors of amyloid beta-protein precursor processing. J. Biomol. Screen. 10: 1-12. ... Natural oligomers of the amyloid-beta protein specifically disrupt cognitive function. Nat. Neurosci. 8: 79-84.. Lesne, S., M. ... where his research group focuses on the amyloid precursor protein (APP), the neurobiology of signaling in the brain, and the ... A specific amyloid-β protein assembly in the brain impairs memory. Nature 440: 352-357.. Ramsden, M., L. Kotilinek, C. Forster ...
https://www.nyas.org/ebriefings/neurodegenerative-diseases/
Modulation of β-amyloid precursor protein trafficking and processing by the low density lipoprotein receptor family<...
Amyloid beta-Protein Precursor Medicine & Life Sciences 66% * low density lipoprotein receptor-related protein 8 Medicine & ... Aβ is produced by proteolytic processing of a transmembrane protein, β-amyloid precursor protein (APP), by β- and γ-secretases ... Aβ is produced by proteolytic processing of a transmembrane protein, β-amyloid precursor protein (APP), by β- and γ-secretases ... Aβ is produced by proteolytic processing of a transmembrane protein, β-amyloid precursor protein (APP), by β- and γ-secretases ...
https://mayoclinic.pure.elsevier.com/en/publications/modulation-of-%CE%B2-amyloid-precursor-protein-trafficking-and-process
Tilo Kunath - Research output - University of Edinburgh Research Explorer
Amyloid beta-Protein Precursor 100% * Neurons 53% * Induced Pluripotent Stem Cells 24% ... Amyloid precursor protein expression and processing are differentially regulated during cortical neuron differentiation. ... Multiomics analyses of HNF4a protein domain function during human pluripotent stem cell differentiation. Wang, Y., Tatham, M. H ... Sideroflexin 3 is a α-synuclein-1 dependent mitochondrial protein 2 that regulates synaptic morphology. Amorim, I., Graham, L. ...
https://www.research.ed.ac.uk/en/persons/tilo-kunath/publications/
Alzheimer Disease Clinical Presentation: History, Physical Examination, Stages of Alzheimer DiseaseAlzheimer Disease Clinical Presentation: History, Physical Examination, Stages of Alzheimer Disease
The fetal basis of amyloidogenesis: exposure to lead and latent overexpression of amyloid precursor protein and beta-amyloid in ... Long-term accumulation of amyloid-beta, beta-secretase, presenilin-1, and caspase-3 in damaged axons following brain trauma. Am ... The beta-amyloid fragments begin coming together into clumps outside the cell, then join other molecules and non-nerve cells to ... New perspectives on amyloid-beta dynamics after acute brain injury: moving between experimental approaches and studies in the ...
https://www.medscape.com/answers/1134817-22570/what-is-the-presentation-of-severe-alzheimer-disease-ad
The neurogenomic transition from territory establishment to parenting in a territorial female songbird | BMC Genomics | Full...The neurogenomic transition from territory establishment to parenting in a territorial female songbird | BMC Genomics | Full...
... most notably amyloid beta precursor protein (APP) (Fig. 2). The VmT and HYPO shared 55 DEG (Fig. 1a), and the log2 fold change ... Protein kinases, such as those involved in the MAPK signaling pathway found here, are also implicated in the control of ... Boseret G, Ball GF, Balthazart J. The microtubule-associated protein doublecortin is broadly expressed in the telencephalon of ... neuropeptide VF precursor; NPVF) or have unknown functions in the brain (luteinizing hormone receptor; LHCGR [76]). This ...
https://bmcgenomics.biomedcentral.com/articles/10.1186/s12864-019-6202-3
alzheimers-diseasealzheimers-disease
Nonamyloidogenic processing of amyloid beta precursor protein is associated with retinal function improvement in aging male APP ... Joly S, Lamoureux S, Pernet V (2017) Nonamyloidogenic processing of amyloid beta precursor protein is associated with retinal ... Objective: To determine amyloid beta role in the aging retina in Alzheimers Disease ... Expression of regulator of G-protein signaling 14 of 414 amino acids (RGS14414) restored ORM in memory-deficient PRh-lesioned ...
https://atsbio.com/kb-tags/alzheimers-disease/
Simple model systems: a challenge for Alzheimers disease | SpringerLinkSimple model systems: a challenge for Alzheimer's disease | SpringerLink
The discovery of specific genes and proteins associated with AD, and the development of new technologies for the production of ... the amyloid precursor protein (APP). According to the amyloid hypothesis cascade, the beta-amyloid (Aβ) peptide deposits are ... Daigle I, Li C: apl-1, a Caenorhabditis elegans gene encoding a protein related to the human beta-amyloid protein precursor. ... Plaques are formed mostly from the deposition of amyloid beta (Ab) a peptide derived from amyloid precursor protein (APP). The ...
https://link.springer.com/article/10.1186/1742-4933-9-3
KEGG VARIANT: 351v1KEGG VARIANT: 351v1
Early-onset Alzheimers disease caused by mutations at codon 717 of the beta-amyloid precursor protein gene. ... In vitro studies of amyloid beta-protein fibril assembly and toxicity provide clues to the aetiology of Flemish variant (Ala692 ... nt06412 Unfolded protein response (UPR) signaling. nt06414 Apoptosis. nt06417 AGE-RAGE signaling. nt06418 Oxidative ...
https://www.kegg.jp/entry/hsa_var:351v1
Turmeric Produces Remarkable Recovery in Alzheimers PatientsTurmeric Produces 'Remarkable' Recovery in Alzheimer's Patients
Curcumin decreases amyloid-beta peptide levels by attenuating the maturation of amyloid-beta precursor protein. ... The inhibitory effects of different curcuminoids onβ-amyloid protein, β-amyloid precursor protein and β-site amyloid precursor ... Curcumin inhibits formation of amyloid beta oligomers and fibrils, binds plaques, and reduces amyloid in vivo. Neurochem Int. ... possessing neuroprotective-neurorescue and amyloid precursor protein-processing regulatory activities as therapeutic agents. ...
https://greenmedinfo.com/blog/turmeric-produces-remarkable-recovery-alzheimers-patients
Kelly L Jordan-sciutto | Faculty | About Us | Perelman School of Medicine | Perelman School of Medicine at the University of...
HIV Protease Inhibitors Alter Amyloid Precursor Protein Processing via beta-Site Amyloid Precursor Protein Cleaving Enzyme-1 ... beta-amyloid, and HIV-infected macrophage supernatant. These studies are aimed at determining how cell cycle proteins regulate ... 5. Regulation of Nrf2 nuclear transport in neurons responding to oxidative stress, beta amyloid, neuroprotective factors, and ... Jordan-Sciutto, K. L.: Serum amyloid A: an ozone-induced circulating factor with potentially important functions in the lung- ...
https://www.med.upenn.edu/apps/faculty/index.php/g293/p4380730
Publications from CCI Users and Staff | University of GothenburgPublications from CCI Users and Staff | University of Gothenburg
"Beta-Amyloid Precursor Protein-B Is Essential for Mauthner Cell Development in the Zebrafish in a Notch-Dependent Manner." Dev ... Title: The physiological processing of Alzheimer-associated amyloid beta precursor protein in human and animal-derived neuronal ... The zebrafish amyloid precursor protein-b is required for motor neuron guidance and synapse formation. Abramsson A, Kettunen P ... "Amyloid Precursor Protein Expression and Processing Are Differentially Regulated During Cortical Neuron Differentiation." Sci ...
https://www.gu.se/en/core-facilities/centre-for-cellular-imaging/publications-from-cci-users-and-staff
Neuroprotective role of MMP-9 overexpression in the brain of Alzheimers 5xFAD mice<...Neuroprotective role of MMP-9 overexpression in the brain of Alzheimer's 5xFAD mice<...
Amyloid beta-Protein Precursor Medicine & Life Sciences 21% * Brain-Derived Neurotrophic Factor Medicine & Life Sciences 19% ... In the non-amyloidogenic pathway, the amyloid-β precursor protein (APP) is cleaved within the Aβ peptide sequence by α- ... In the non-amyloidogenic pathway, the amyloid-β precursor protein (APP) is cleaved within the Aβ peptide sequence by α- ... In the non-amyloidogenic pathway, the amyloid-β precursor protein (APP) is cleaved within the Aβ peptide sequence by α- ...
https://experts.umn.edu/en/publications/neuroprotective-role-of-mmp-9-overexpression-in-the-brain-of-alzh
Involvement of Free Radicals in the Development and Progression of Alzheimers Disease | IntechOpenInvolvement of Free Radicals in the Development and Progression of Alzheimer's Disease | IntechOpen
βA1-42 results from hydrolysis of the amyloid precursor protein by β-secretase in a process known as the amyloidogenic pathway ... proteins, and nucleic acids, thereby contributing to neurodegeneration. In addition, βA1-42 is recognized by microglial ... Amyloid beta-peptide of 42 amino acid residues (Aβ1-42) is the main source of FRs in patients with AD. ... Coordination of redox active metal ions to the amyloid precursor protein and to amyloid-beta peptides involved in Alzheimer ...
https://www.intechopen.com/chapters/52065
Notch signaling functions in noncanonical juxtacrine manner in platelets to amplify thrombogenicity | eLifeNotch signaling functions in noncanonical juxtacrine manner in platelets to amplify thrombogenicity | eLife
Characterization of platelet-releasable forms of beta-amyloid precursor proteins: the effect of thrombin ... 2001) Amyloid precursor protein and amyloid β peptide in human platelets Journal of Biological Chemistry 276:17036-17043. ... "involvement of γ-secretase in the cleavage of cleavage of amyloid-precursor proteins (APP) releasing amyloid-β (Aβ), etc." to ... "involvement of γ-secretase in the cleavage of cleavage of amyloid-precursor proteins (APP) releasing amyloid-β (Aβ), etc." to ...
https://elifesciences.org/articles/79590
ProteolyticPeptidesAccumulationCleavageMutationDepositionLevels of beta-amyloidPlaquesAbetaSoluble amyloidMembraneNeuronalNeurofibrillary tanglesAlzheimer's DiseaseSequentialMetabolismProteolysisBrainAlzheimer DiseaseCodonHypothesisSecretasesGeneReceptorsEnzymeSynapticIntracellularAmino acidMutationsCleavesDiseaseDepositsPathologyPathwayPolypeptideVitro1991IncreasesNeurodegenerationBurden2017MRNA and proteinAmyloidogenicUrineAggregate
Proteolytic7
  • These neurotoxic peptides are generated from the amyloid precursor protein via sequential cleavage by β- and γ-secretases in the 'amyloidogenic' proteolytic pathway. (lancs.ac.uk)
  • Amyloid beta peptide (Abeta), generated by proteolytic cleavage of the amyloid precursor protein (APP), is central to AD pathogenesis. (rcsb.org)
  • The proteolytic processing of the precursor protein beta-amyloid. (news-medical.net)
  • Moreover, proteolytic processing of Alc proteins appears highly similar to that of APP. (elsevier.com)
  • Amyloid-β peptide (Aβ) accumulation in the brain is an early, toxic event in the pathogenesis of Alzheimer's disease (AD), Aβ is produced by proteolytic processing of a transmembrane protein, β-amyloid precursor protein (APP), by β- and γ-secretases. (elsevier.com)
  • 1991 ) Alzheimer beta/A4 amyloid precursor protein in human brain: aging-associated increases in holoprotein and in a proteolytic fragment. (neurotree.org)
  • BACE1_HUMAN ] Responsible for the proteolytic processing of the amyloid precursor protein (APP). (proteopedia.org)
Peptides7
  • The amyloid cascade hypothesis proposes that excessive accumulation of amyloid beta-peptides is the initiating event in Alzheimer's disease. (lancs.ac.uk)
  • In SH-SY5Y neuroblastoma cells, dichloroacetate enhanced sAPPα generation whilst inhibiting β-secretase processing of endogenous amyloid precursor protein and the subsequent generation of amyloid beta-peptides. (lancs.ac.uk)
  • Single beta-amyloid peptides, after misfolding, can aggregate and form fibrils and successively plaques. (springer.com)
  • It is cleaved by AMYLOID PRECURSOR PROTEIN SECRETASES to produce peptides of varying amino acid lengths. (bvsalud.org)
  • A 39-42 amino acid peptide, AMYLOID BETA-PEPTIDES is a principal component of the extracellular amyloid in SENILE PLAQUES . (bvsalud.org)
  • The common precursor polypeptide of pancreatic GLUCAGON and intestinal GLUCAGON-LIKE PEPTIDES. (bvsalud.org)
  • [ 138 , 139 , 140 ] The author's studies determined the ability of these various candidate beta-sheet breaker peptides to inhibit amyloidlike fibril formation of PrP109-141 using a fluorometric assay based on the fluorescence emission of thioflavine T. (medscape.com)
Accumulation4
  • Together, these results suggest that dietary DHA could be protective against β-amyloid production, accumulation, and potential downstream toxicity. (jneurosci.org)
  • Accumulation of amyloid-β (Αβ) peptide is believed to play a central role in the pathogenesis of Alzheimer's disease (AD). (umn.edu)
  • Copper exposure resulted in altered accumulation of a precursor protein that produces beta amyloid brain plaque as well as tau protein. (knowledgeofhealth.com)
  • This mutation causes increased accumulation of amyloid-beta protein in the walls of cerebral arteries and capillaries. (cdc.gov)
Cleavage8
  • Presenilin-dependent gamma-secretase processing of beta-amyloid precursor protein at a site corresponding to the S3 cleavage of Notch. (escholarship.org)
  • The similar gamma-secretase cleavage of the beta-amyloid precursor protein (betaAPP) results in the secretion of amyloid beta-peptide (Abeta). (escholarship.org)
  • However, the magnitudes of C-terminal alteration of p3-Alc α , p3-Alc β , and p3-Alc γ were not equivalent, suggesting that one type of γ-secretase dysfunction does not appear in the phenotype equivalently in the cleavage of type I membrane proteins. (elsevier.com)
  • The metabolic processing of APP that results in Ab formation requires two enzymatic cleavage events, a b-secretase cleavage by the aspartyl protease beta-site APP-cleaving enzyme (BACE) and a g-secretase cleavage dependent on presenilin. (springer.com)
  • Cleavage of APP at the N-terminus of the A beta peptide by beta-secretase and at the C-terminus by one or more gamma-secretases constitutes the beta-amyloidogenic pathway, i.e. the pathway by which A beta is formed. (justia.com)
  • Cleavage of APP by alpha-secretase produces alpha-sAPP, a secreted form of APP that does not result in beta-amyloid plaque formation. (justia.com)
  • An aspartyl protease has been identified as the enzyme responsible for processing of APP at the beta-secretase cleavage site. (justia.com)
  • Caspase 3 participates in cleavage of Amyloid beta 4A precursor protein which is implicated with neuronal death Alzheimer's disease. (neuromics.com)
Mutation5
  • These R1.40 transgenic mice express all mRNA and protein isoforms of the human amyloid beta (A4) precursor protein APP containing the Familial Alzheimer's Disease (FAD) Swedish mutation K670N/M671L. (mmrrc.org)
  • A 650 kb YAC transgene containing the entire human amyloid beta (A4) precursor protein (APP) gene, and approximately 250 kb of flanking sequence, was altered to include the Swiss mutation K670N/M671L associated with Familial Alzheimer's Disease (FAD). (mmrrc.org)
  • Most forms of HCHWA (Dutch, Arctic, Piedmont, Iowa, Flemish and Italian) are due to a point-mutation in the APP gene on chromosome 21q21.2, which encodes the beta-amyloid precursor protein. (cdc.gov)
  • Only one form of HCHWA, Icelandic type, is due to a mutation in the CST3 gene on chromosome 20p11.2, encoding the precursor protein cystatin C. (cdc.gov)
  • The researchers found that the man had a mutation in a gene coding for a protein called reelin, which is associated with brain disorders including schizophrenia and autism. (cdc.gov)
Deposition7
  • Therefore, APP processing and amyloid beta metabolism and deposition are modified by the genetic background. (mmrrc.org)
  • Plaques are formed mostly from the deposition of amyloid beta (Ab) a peptide derived from amyloid precursor protein (APP). (springer.com)
  • The number of reactive astrocytes increases in AD, phagocytizing and reducing amyloid β (Aβ) deposition because these cells surround amyloid plaques and secrete proinflammatory factors [ 13 , 14 ]. (medsci.org)
  • These compounds include inhibitors of the beta-secretase enzyme that are useful in the treatment of Alzheimer's disease and other diseases characterized by deposition of A beta peptide in a mammal. (justia.com)
  • Deposition of A beta in areas of the brain responsible for cognitive activities is a major factor in the development of AD. (justia.com)
  • Several lines of evidence indicate that progressive cerebral deposition of beta-amyloid peptide (A beta) plays a seminal role in the pathogenesis of AD and can precede cognitive symptoms by years or decades. (justia.com)
  • Describes a group of rare familial central nervous system disorders characterised by amyloid deposition in the cerebral blood vessels leading to haemorrhagic and non-haemorrhagic strokes, focal neurological deficits, and progressive cognitive decline eventually leading to dementia. (cdc.gov)
Levels of beta-amyloid3
  • Recent studies have shown that lack of sleep, for even one night, can significantly increase levels of beta-amyloid in the brain - one of the main toxic proteins that are linked to Alzheimer's disease. (news-medical.net)
  • During sleep, the brain uses its own glymphatic system (the brain's own drainage system) to wash out excessive levels of beta-amyloid and other metabolites that accumulate. (news-medical.net)
  • Aluminum increases levels of beta-amyloid and ubiquitin in neuroblastoma but not in glioma cells. (cdc.gov)
Plaques10
  • Recent studies indicated that GSK3 also involved in the formation of Alzheimer's disease (AD) pathologies: neurofibrillary tangles and amyloid plaques. (ubc.ca)
  • Neurofibrillary tangles develop when abnormal tau proteins accumulate inside neurons and form insoluble filaments, and amyloid plaques develop when the amyloid β protein (Aβ) accumulates in increasingly insoluble forms. (ubc.ca)
  • The morphologic features observed in AD patients at autopsy include both extracellular amyloid deposits as amyloid senile plaques and intracellular neurofibrillary tangles (NFT). (springer.com)
  • The prominent features of AD include amyloid plaques, intraneuronal tangles, cell death, inflammatory changes and oxidative stress [ 2 , 3 , 4 ]. (medsci.org)
  • More specifically, it relates to such compounds that are capable of inhibiting beta-secretase, an enzyme that cleaves amyloid precursor protein to produce amyloid beta peptide (A beta), a major component of the amyloid plaques found in the brains of Alzheimer's sufferers. (justia.com)
  • Alzheimer's disease is characterized by two major pathologic observations in the brain: neurofibrillary tangles and beta amyloid (or neuritic) plaques, comprised predominantly of an aggregate of a peptide fragment know as A beta. (justia.com)
  • Individuals with AD exhibit characteristic beta-amyloid deposits in the brain (beta amyloid plaques) and in cerebral blood vessels (beta amyloid angiopathy) as well as neurofibrillary tangles. (justia.com)
  • Amyloidogenic plaques and vascular amyloid angiopathy also characterize the brains of individuals with Trisomy 21 (Down's Syndrome), Hereditary Cerebral Hemorrhage with Amyloidosis of the Dutch-Type (HCHWA-D), and other neurodegenerative disorders. (justia.com)
  • Beta-amyloid plaques are predominantly composed of amyloid beta peptide (A beta, also sometimes designated betaA4). (justia.com)
  • The study challenges the theory that Alzheimer's disease is primarily driven by amyloid plaques, which are the targets of several drugs recently approved by the US Food and Drug Administration. (cdc.gov)
Abeta3
  • 2017) The diphenylpyrazole compound anle138b blocks Abeta channels and rescues disease phenotypes in a mouse model for amyloid pathology. (tu-braunschweig.de)
  • Amyloid-beta (Abeta) is a 36-43 amino acid peptide that is derived by processing of the beta-amyloid precursor protein (APP). (nel.edu)
  • At a low concentration (10 uM), aluminum sulfate stimulated the level of immunoreactive Abeta and ubiquitin in NBP2 cells without changing the levels of the amyloid precursor protein (APP). (cdc.gov)
Soluble amyloid3
  • Alternatively, the amyloid precursor protein can be processed via the 'non-amyloidogenic' pathway which, through the action of the α-secretase a disintegrin and metalloproteinase (ADAM) 10, both precludes amyloid beta-peptide formation and has the additional benefit of generating a neuroprotective soluble amyloid precursor protein fragment, sAPPα. (lancs.ac.uk)
  • Homocysteine metabolism is associated with cerebrospinal fluid levels of soluble amyloid precursor protein and amyloid beta. (cdc.gov)
  • High Soluble Amyloid-?42 Predicts Normal Cognition in Amyloid-Positive Individuals with Alzheimer's Disease-Causing Mutations. (cdc.gov)
Membrane4
  • Alcadeins (Alcs) constitute a family of neuronal type I membrane proteins, designated Alc α , Alc β , and Alc γ . (elsevier.com)
  • The main constituent of the amyloid deposits is an amphiphilic peptide, derived by proteolysis from a large membrane spanning precursor protein, the amyloid precursor protein (APP). (springer.com)
  • Glucose is the main energy source used by brain cells and its transport across the plasma membrane is mediated by a specific family of membrane proteins known as glucose transporters (GLUTs) ( Shepherd and Kahn, 1999 ). (frontiersin.org)
  • A single-pass type I membrane protein. (bvsalud.org)
Neuronal8
  • We are specifically interested in the role of cell cycle proteins, the endogenous antioxidant response and the endoplasmic reticulum stress response in neuronal dysfunction and damage. (upenn.edu)
  • We hypothesize that neuronal response to these neurodegenerative stimuli includes alterations in expression and/or activity of cell cycle proteins. (upenn.edu)
  • These studies are aimed at determining how cell cycle proteins regulate neuronal survival in response to varied and conflicting stimuli. (upenn.edu)
  • Interestingly, neurons responding to HIV-infected macrophage supernatants (our in vitro model of neuronal response to inflammatory infiltrate which mediates HIV encephalitis) activate calpain and increase E2F1 protein levels. (upenn.edu)
  • In the present study, we demonstrate that neuronal overexpression of MMP-9 in a transgenic AD mouse model harboring five familial AD-related mutations (5xFAD) resulted in increased sAPPα levels and decreased Aβ oligomers without affecting amyloid plaque load in the brain. (umn.edu)
  • Korte M (2019) Neuronal function of Alzheimer's protein. (tu-braunschweig.de)
  • 1989 ) An analysis of postmortem brain samples from 32 alcoholic and nonalcoholic individuals for protein III, a neuronal phosphoprotein. (neurotree.org)
  • Data from our laboratory demonstrated that astrocytes increase neuronal viability and mitochondrial biogenesis, protecting from oxidative stress and inflammation induced by toxic amyloid peptide [ 7 , 8 ]. (medsci.org)
Neurofibrillary tangles1
  • Filamentous neurofibrillary tangles (NTF) are formed from paired helical filaments composed of hyperphosphorylated tau protein, a microtubule-associated protein. (springer.com)
Alzheimer's Disease11
  • Early-onset Alzheimer's disease caused by mutations at codon 717 of the beta-amyloid precursor protein gene. (kegg.jp)
  • Two of these studies are particularly promising, as they reveal that curcumin is capable of enhancing the clearance of the pathological amyloid-beta plaque in Alzheimer's disease patients, [6] and that in combination with vitamin D3 the neurorestorative process is further enhanced. (greenmedinfo.com)
  • [7] Additional preclinical research indicates curcumin (and its analogs) has inhibitory and protective effects against Alzheimer's disease associated β-amyloid proteins. (greenmedinfo.com)
  • Currently we are focusing our research efforts on the role of cell cycle proteins, the endogenous antioxidant response and unfolded protein response in three neurodegenerative disorders: HIV encephalitis (HIVE), Alzheimer's disease (AD), and Parkinson's disease (PD). (upenn.edu)
  • Parkinson's disease (PD) and Alzheimer's disease (AD) share pathological features, including amyloid-beta pathology. (uib.no)
  • For Alzheimer's disease (AD), the focus is the amyloid beta peptide (Aß) that mediates familial Alzheimer's disease pathology. (plos.org)
  • A recent report published in the Archives of Medical Research says: "In the case of Alzheimer's disease, amyloid-β metabolism and tau protein have been exhaustively studied, both to no avail. (knowledgeofhealth.com)
  • The clinical trial demonstrates that long-term oral intake of 8 mg of copper can be excluded as a risk factor for Alzheimer's disease based on the measure of beta amyloid and tau protein in cerebral spinal fluid. (knowledgeofhealth.com)
  • We still believe amyloid plays an important but complex role in Alzheimer's disease," David Reese, MD, executive vice president of Research and Development at Amgen, said in a statement. (medscape.com)
  • Umibecestat joins a host of other amyloid-focused drugs that have failed to demonstrate a benefit in Alzheimer's disease. (medscape.com)
  • Alzheimer's Disease and Amyloid: Time to Move On? (medscape.com)
Sequential1
  • The Aβ peptide is generated through sequential cleavages of the β-amyloid precursor protein by β-secretase (BACE1) and γ-secretase. (ubc.ca)
Metabolism5
  • However, given that age is the greatest risk factor for AD, we explored an alternative drug discovery scheme that is based upon efficacy in multiple cell culture models of age-associated pathologies rather than exclusively amyloid metabolism. (plos.org)
  • The assays include the loss of trophic support, oxidative stress, the reduction of energy metabolism ( in vitro ischemia and glucose starvation) and amyloid toxicity. (plos.org)
  • The kidney is the major site of metabolism of light-chain proteins. (medscape.com)
  • Metabolism (catabolism) of these filtered light-chain proteins depends on normal proximal tubular cell function, and damage to these cells can result in increased excretion of light-chain proteins in the urine. (medscape.com)
  • involved PARs cyanide via G effectiveness histone( 4) and via the metabolism: system fructose of the G-protein( 5). (erik-mill.de)
Proteolysis5
  • In the current study, we investigated whether the orphan drug, dichloroacetate, could alter amyloid precursor protein proteolysis. (lancs.ac.uk)
  • Similar enhancement of ADAM-mediated amyloid precursor protein processing by dichloroacetate was observed in unrelated cell lines and the effect was not exclusive to the amyloid precursor protein as an ADAM substrate, as indicated by dichloroacetate-enhanced proteolysis of the Notch ligand, Jagged1. (lancs.ac.uk)
  • Despite altering proteolysis of the amyloid precursor protein, dichloroacetate did not significantly affect the expression/activity of α-, β- or γ-secretases. (lancs.ac.uk)
  • In conclusion, dichloroacetate can inhibit amyloidogenic and promote non-amyloidogenic proteolysis of the amyloid precursor protein. (lancs.ac.uk)
  • A beta peptide is derived by proteolysis of the amyloid precursor protein (APP) and is comprised of 39-42 amino acids. (justia.com)
Brain18
  • However, during sleeplessness and lack of overall sleep (even as little as one night), the brain is not able to clear out beta-amyloid levels effectively, and thus levels can build up over time. (news-medical.net)
  • Therefore, people suffering from insomnia should seek medical advice as soon as possible in order to delay or lower the amyloid burden in the brain. (news-medical.net)
  • The Alcs express in neurons dominantly and largely colocalize with the Alzheimer amyloid precursor protein (APP) in the brain. (elsevier.com)
  • Transgene expression (mRNA and full-length protein) is 2 to 3 fold the wild-type mouse App expression level in the hemizygous state in brain tissue as revealed by RT-PCR and Western Blot analysis. (mmrrc.org)
  • Functionally, overexpression of MMP-9 prevented the cognitive deficits displayed by 5xFAD mice, an improvement that was accompanied by increased levels of the pre-synaptic protein synaptophysin and mature brain-derived neurotrophic factor (BDNF) in the brain. (umn.edu)
  • We also evaluated brain expression of Glucose Transporter (GLUT) proteins given their role in transmembrane glucose transport in neurons and microglial cells during stress conditions [ 16 ]. (biomedcentral.com)
  • Lab animals given drinking water with copper experienced measurable acceleration of brain plaque like beta amyloid whereas animals given filtered water did not. (knowledgeofhealth.com)
  • Crystal Structure of a cycloamide-urethane-derived novel inhibitor bound to human brain memapsin 2 (beta-secretase). (proteopedia.org)
  • Cycloamide-urethanes containing 14- to 16-membered rings exhibited low nanomolar inhibitory potencies against human brain memapsin 2 (beta-secretase). (proteopedia.org)
  • Structure-based design of cycloamide-urethane-derived novel inhibitors of human brain memapsin 2 (beta-secretase). (proteopedia.org)
  • Ghosh AK, Devasamudram T, Hong L, DeZutter C, Xu X, Weerasena V, Koelsch G, Bilcer G, Tang J. Structure-based design of cycloamide-urethane-derived novel inhibitors of human brain memapsin 2 (beta-secretase). (proteopedia.org)
  • To explore the underlying synaptic basis of these effects, excitatory synapses represented by postsynaptic density protein-95 (PSD-95) were immunolabelled on a series of brain sections and stereologically quantified in the dorsomedial striatum (DMS) and dorsolateral striatum (DLS), as well as in area CA1 of the dorsal hippocampus. (bvsalud.org)
  • Post-mortem autoptic analysis shows the presence of amyloid ß deposits, neuroinflammation and severe brain atrophy. (bvsalud.org)
  • If we start with the similarities in neurodegenerative disease (NDS), there are free radicals in the brain, neuroinflammation, proteins / structures that clump together, the cleansing of diseased cells and proteins that fail, dysfunctional synapses and damaged nerve cells / nerve tissue. (foodpharmacyco.com)
  • Alzheimer's is the most common type of dementia where unhealthy proteins accumulate in the brain and the neurotransmitter acetylcholine decreases. (foodpharmacyco.com)
  • In a healthy brain, unhealthy proteins are cleaned away, but in the brain of someone with Alzheimer's, this cleaning does not work, and so these levels build up over the years. (foodpharmacyco.com)
  • A similar story with neuroinflammation and unhealthy proteins that clump together in the brain and disrupt neurons. (foodpharmacyco.com)
  • The drugs effectively remove amyloid from the brain, but lead to only a moderate improvement in rates of cognitive decline. (cdc.gov)
Alzheimer Disease2
  • Copernicus revisited: amyloid beta in alzheimer disease. (ucsd.edu)
  • The pathogenesis of Alzheimer disease: an alternative to the amyloid hypothesis. (ucsd.edu)
Codon1
  • The formation of intracellular amyloid-like inclusions by mutant proteins is a feature of two groups of codon reiteration diseases, for which there are currently no treatments. (bmj.com)
Hypothesis1
  • According to the amyloid hypothesis cascade, the beta-amyloid (Aβ) peptide deposits are the fundamental cause of the disease [ 1 ]. (springer.com)
Secretases1
  • In the non-amyloidogenic pathway, the amyloid-β precursor protein (APP) is cleaved within the Aβ peptide sequence by α-secretases, giving rise to the potent neurotrophic N-terminal fragment sΑPPα. (umn.edu)
Gene1
  • A total of 451 sEOAD samples were screened for known causative mutations in exons 16 and 17 of the amyloid precursor protein (APP) gene. (nih.gov)
Receptors2
  • The filtered light-chain proteins, reabsorbed by the proximal tubular cells via the tandem megalin/cubilin receptors, are catabolized by lysosomal enzymes. (medscape.com)
  • reabsorption chaperones via precursor virus Protease Activated Receptors( PARs). (erik-mill.de)
Enzyme4
  • The beta-secretase enzyme has been disclosed using varied nomenclature, including BACE, Asp, and Memapsin. (justia.com)
  • Umibecestat is a small molecule inhibitor of the beta-site amyloid precursor protein-cleaving enzyme 1 (BACE1). (medscape.com)
  • Description: This is Double-antibody Sandwich Enzyme-linked immunosorbent assay for detection of Human Tubulin Polymerization Promoting Protein (TPPP) in tissue homogenates, cell lysates and other biological fluids. (1elisakits.com)
  • Description: Enzyme-linked immunosorbent assay based on the Double-antibody Sandwich method for detection of Human Tubulin Polymerization Promoting Protein (TPPP) in samples from tissue homogenates, cell lysates and other biological fluids with no significant corss-reactivity with analogues from other species. (1elisakits.com)
Synaptic2
  • Using this approach, we identified an exceptionally potent, orally active, neurotrophic molecule that facilitates memory in normal rodents, and prevents the loss of synaptic proteins and cognitive decline in a transgenic AD mouse model. (plos.org)
  • The proteins beta-amyloid form plaque, and tau form the ball which lead to dysfunctional neuron function, abnormal synaptic transmission, neuroinflammation and eventually neuron death. (foodpharmacyco.com)
Intracellular2
  • Intracellular amyloid-like inclusions formed by mutant proteins result from polyglutamine expansions in Huntington's disease (HD) and polyalanine expansions in polyadenine binding protein 2 (PABP2) in oculopharyngeal muscular dystrophy (OPMD). (bmj.com)
  • While storage and release of lipids are major functions of adipocytes, the adipocyte also uses specific lipid molecules for intracellular signaling and uses a host of protein factors to communicate with essentially every organ system in the body. (diabetesjournals.org)
Amino acid1
  • Amyloid beta-peptide of 42 amino acid residues (Aβ1-42) is the main source of FRs in patients with AD. (intechopen.com)
Mutations1
  • We demonstrate here that variant p3-Alc C termini are modulated by FAD-linked presenilin 1 mutations increasing minor β-amyloid species Aβ42, and these mutations alter the level of minor p3-Alc species. (elsevier.com)
Cleaves2
  • Cleaves at the N-terminus of the A-beta peptide sequence, between residues 671 and 672 of APP, leads to the generation and extracellular release of beta-cleaved soluble APP, and a corresponding cell-associated C-terminal fragment which is later released by gamma-secretase. (proteopedia.org)
  • Lin X, Koelsch G, Wu S, Downs D, Dashti A, Tang J. Human aspartic protease memapsin 2 cleaves the beta-secretase site of beta-amyloid precursor protein. (proteopedia.org)
Disease5
  • Beta-amyloid is a defining feature of AD, now believed to be a causative precursor or factor in the development of disease. (justia.com)
  • Brookmeyer, R et al,2007).Alzheimer 's disease is a type of a protein misfolding disease, caused by accretion of abnormally folded amyloid-beta and tau proteins in the encephalon. (freebooksummary.com)
  • Genetic and transgenic studies are consistent with a model where expanded polyglutamines cause disease by conferring a novel toxic function on the disease proteins. (bmj.com)
  • Thus, disease is associated with expansions of 12 or more uninterrupted alanines in this nuclear protein. (bmj.com)
  • Inhibiting AKT with MK-2206 or MEK1/2 with U0126 for 24 hours in the absence of R5020 increased total and nuclear PRA and PRB protein levels in OSIS but not in eutopic endometrial stromal cells from disease-free patients from disease-free patients. (webpediatrica.com)
Deposits1
  • in contrast to 14 month old homozygous B6-R1.40 mice, homozygous D2-R1.40 and 129S1-R1.40 mice do not develop amyloid beta deposits in the parietal or frontal cortex even by 20 months of age. (mmrrc.org)
Pathology1
  • Furthermore, the elevations in beta-amyloid were shown to be accentuated in areas that are damaged in early Alzheimer's pathology, such as the hippocampus and the thalamus (involved in memory, for example). (news-medical.net)
Pathway3
  • Our investigation of E2F1 has resulted in the discovery of a role for this protein in activation of a calpain-dependent death pathway which has not been previously described. (upenn.edu)
  • βA1-42 results from hydrolysis of the amyloid precursor protein by β-secretase in a process known as the amyloidogenic pathway. (intechopen.com)
  • This alternate pathway precludes the formation of A beta peptide. (justia.com)
Polypeptide2
  • Another AD hallmark are the NFT, composed by neurofilaments and hyperphosphorylated tau protein, a microtubule associated polypeptide. (springer.com)
  • The specific sequence of amino acids determines the shape the polypeptide will take, during protein folding, and the function of the protein. (lecturio.com)
Vitro2
  • In vitro models of neurodegeneration in each of these diseases also exhibit alterations in cell cycle protein subcellular localization. (upenn.edu)
  • In vitro findings are then used to assess potential roles for these proteins in animal models as well as autopsy tissue relevant to each neurodegenerative condition. (upenn.edu)
19911
  • problems are G-protein associated rounds secreted by a Cerebrotendinous aggregation in an human ICA( Vu, 1991)( 3). (erik-mill.de)
Increases2
  • Those who were sleep-deprived the most (who had the highest increases in beta-amyloid in the thalamus) also often experienced worse moods. (news-medical.net)
  • Whether sustained normocortisolism induced by medical therapy induces re-expression of functional sst 2 protein in corticotroph adenomas and whether this increases the ACTH-lowering potency of octreotide remains to be established. (webpediatrica.com)
Neurodegeneration1
  • Cam, JA & Bu, G 2006, ' Modulation of β-amyloid precursor protein trafficking and processing by the low density lipoprotein receptor family ', Molecular neurodegeneration , vol. 1, no. 1, 8. (elsevier.com)
Burden1
  • Because effects of DHA on Alzheimer pathogenesis, particularly on amyloidosis, are unknown, we used the APPsw (Tg2576) transgenic mouse model to evaluate the impact of dietary DHA on amyloid precursor protein (APP) processing and amyloid burden. (jneurosci.org)
20171
  • Müller UC, Deller T, Korte M (2017) Not just amyloid: physiological functions of the amyloid precursor protein family. (tu-braunschweig.de)
MRNA and protein2
  • We evaluated receptor mRNA and protein expression levels and effects of octreotide, pasireotide, and cabergoline on ACTH secretion by cultured human corticotroph adenoma cells. (webpediatrica.com)
  • Real-time PCR and Western blotting were used to assess mRNA and protein expression of cartonectin. (webpediatrica.com)
Amyloidogenic1
  • Over-expression of the amyloid precursor protein partly ablated the effect of dichloroacetate on amyloidogenic and non-amyloidogenic processing whilst over-expression of the β-secretase only ablated the effect on amyloidogenic processing. (lancs.ac.uk)
Urine4
  • Plasma cells normally produce a slight excess of light chains that are either excreted or catabolized by the kidney, and only a minute amount of light-chain protein normally appears in the urine. (medscape.com)
  • Light-chain proteins appear in urine in high concentration either when the production of light-chain proteins is markedly increased or when the ability of the proximal tubules to reabsorb all the filtered protein is diminished. (medscape.com)
  • The presence of light-chain proteins in the urine is associated with a number of systemic diseases (see Etiology ). (medscape.com)
  • This process is exceedingly efficient, and only a minute amount of light-chain protein normally appears in the urine. (medscape.com)
Aggregate3
  • In this procedure, the hydrophobic residues of the valine at place 6 of the beta concatenation of HbS associates with the hydrophobic spot, doing the hemoglobin molecules to aggregate and organize hempen precipitates. (freebooksummary.com)
  • 1 Nevertheless, strategies that target protein misfolding frequently reduce aggregate formation and cell death in parallel. (bmj.com)
  • In mammalian cell based models of both polyglutamine and polyalanine diseases, the mutant proteins are much more prone to aggregate formation than their wild-type counterparts and cause significantly more cell death. (bmj.com)
MedlinePlus: Genes
MedlinePlus: Genes (medlineplus.gov)
RCSB PDB - 2FK3: Structure of the Alzheimer's Amyloid Precursor Protein (APP) Copper Binding Domain in 'large unit cell' form
RCSB PDB - 2FK3: Structure of the Alzheimer's Amyloid Precursor Protein (APP) Copper Binding Domain in 'large unit cell' form (rcsb.org)
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Alzheimer's Disease and Sleep Disruption (news-medical.net)
Animal Diseases - Ontology Report - Rat Genome Database
Animal Diseases - Ontology Report - Rat Genome Database (rgd.mcw.edu)
Search Ageing-Associated Genes in Humans
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Human Amyloid beta (A4) Precursor Protein (APP) Protein (Myc-DYKDDDDK Tag), Recombinant | ABIN2714676
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Neurodegenerative Diseases | The New York Academy of Sciences
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Tilo Kunath - Research output - University of Edinburgh Research Explorer
Tilo Kunath - Research output - University of Edinburgh Research Explorer (research.ed.ac.uk)
Alzheimer Disease Clinical Presentation: History, Physical Examination, Stages of Alzheimer Disease
Alzheimer Disease Clinical Presentation: History, Physical Examination, Stages of Alzheimer Disease (medscape.com)
Alzheimer Disease Clinical Presentation: History, Physical Examination, Stages of Alzheimer Disease
Alzheimer Disease Clinical Presentation: History, Physical Examination, Stages of Alzheimer Disease (medscape.com)
Simple model systems: a challenge for Alzheimer's disease | SpringerLink
Simple model systems: a challenge for Alzheimer's disease | SpringerLink (link.springer.com)
Turmeric Produces 'Remarkable' Recovery in Alzheimer's Patients
Turmeric Produces 'Remarkable' Recovery in Alzheimer's Patients (greenmedinfo.com)
Intestinal Enterokinase Deficiency: Background, Pathophysiology, Epidemiology
Intestinal Enterokinase Deficiency: Background, Pathophysiology, Epidemiology (emedicine.medscape.com)
Neurology - Research output - Mayo Clinic
Neurology - Research output - Mayo Clinic (mayoclinic.pure.elsevier.com)
Alzheimer Disease Treatment & Management: Approach Considerations, Treatment of Mild to Moderate Disease, Treatment of Moderate...
Alzheimer Disease Treatment & Management: Approach Considerations, Treatment of Mild to Moderate Disease, Treatment of Moderate... (medscape.com)
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Papaya: MedlinePlus Supplements (medlineplus.gov)
Alzheimer Disease Workup: Approach Considerations, Blood Studies, Brain MRI or CT Scanning
Alzheimer Disease Workup: Approach Considerations, Blood Studies, Brain MRI or CT Scanning (medscape.com)
Alzheimer Disease: Practice Essentials, Background, Anatomy
Alzheimer Disease: Practice Essentials, Background, Anatomy (medscape.com)
Hyperglycaemia and apoptosis of microglial cells in human septic shock | Critical Care | Full Text
Hyperglycaemia and apoptosis of microglial cells in human septic shock | Critical Care | Full Text (ccforum.biomedcentral.com)
Medscape | J Neuroinflammation - Publication Information
Medscape | J Neuroinflammation - Publication Information (medscape.com)
Advances in Exercise, Fitness, and Performance Genomics in 2010
Advances in Exercise, Fitness, and Performance Genomics in 2010 (medscape.com)
IMCD Transcriptome Database
IMCD Transcriptome Database (dir.nhlbi.nih.gov)
(emedicine.medscape.com)