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.
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.
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.
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)
Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.
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.
A plant family of the order Liliales, subclass Liliidae, class Liliopsida (monocotyledon).
Accumulations of extracellularly deposited AMYLOID FIBRILS within tissues.
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)
A sub-subclass of endopeptidases that depend on an ASPARTIC ACID residue for their activity.
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)
The mulberry plant family of the order Urticales, subclass Hamamelidae, class Magnoliopsida. They have milky latex and small, petalless male or female flowers.
A subclass of PEPTIDE HYDROLASES that catalyze the internal cleavage of PEPTIDES or PROTEINS.
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.
A subclass of iridoid compounds that include a glycoside moiety, usually found at the C-1 position.
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.
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.
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.
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.
Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.
Established cell cultures that have the potential to propagate indefinitely.
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.
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.
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.
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.
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.
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.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
The gradual irreversible changes in structure and function of an organism that occur as a result of the passage of time.
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 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.
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.
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.
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.
An acid dye used in testing for hydrochloric acid in gastric contents. It is also used histologically to test for AMYLOIDOSIS.
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.
Proteins prepared by recombinant DNA technology.
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.
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.
The rate dynamics in chemical or physical systems.
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.
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.
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.
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.
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.
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.
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.
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).
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.
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)

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 ...
Anti-β-Amyloid Precursor-Like Protein 1, C-Terminal (643-653) Rabbit pAb - Find MSDS or SDS, a COA, data sheets and more information.
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 ...
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 ...
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 ...
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 - ...
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 ...
APBA2 (amyloid beta precursor protein binding family A member 2), Authors: Dessen P. Published in: Atlas Genet Cytogenet Oncol Haematol.
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 ...
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.
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
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 ...
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 ...
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 ...
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 ...
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.
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 ...
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% ...
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 ...
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 ...
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 ...
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 ...
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 ...
Recombinant Human Amyloid Precursor Protein Protein fragment datasheet (ab124588). Abcam offers quality products including antibodies, assays and other…
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 ...
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 ...
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 ...
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 ...
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 ...
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
APP (Amyloid Precursor Protein), eFluor 570, clone: 22C11, eBioscience™ 100μg; eFluor 570 APP (Amyloid Precursor Protein), eFluor 570, clone: 22C11,...
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 ...
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
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 ...
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, ...
Amyloid beta precursor protein gene (ABPP) encodes a cell surface receptor and transmembrane precursor protein that is cleaved by secretases to form a…
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. ...
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 ...
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 ...
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 ...
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 ...
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). ...
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 ...
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 ...
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 ...
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. ...
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 ...
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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 ...
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.
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
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 ...
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
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 ...
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 ...
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 ...
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 ...
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 ...
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, ...
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 ...
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.
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 ...
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 ...
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. ...
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 ...
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 ...
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 ...
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 ...
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 ...
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
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),
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
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.
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 ...
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 ...
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, ...
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
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 ...
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.
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 ...
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 ...
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 ...
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
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 ...
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 ...
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
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 ...
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 ...
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.
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 ...
Beta-amyloid is a small piece of a larger protein called the amyloid precursor protein (APP). Once APP is activated it is cut ... Mutations to the amyloid beta A4 precursor protein (APP) located on the long arm of chromosome 21 (21q21.3) cause familial ... "Increased β-amyloid release and levels of amyloid precursor protein (APP) in fibroblast cell lines from family members with the ... suggesting that the Asn141Ile mutation alters amyloid precursor protein (APP) metabolism causing an increased rate of protein ...
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: ...
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: ...
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 ...
"Association of a novel human FE65-like protein with the cytoplasmic domain of the beta-amyloid precursor protein". Proceedings ... "Entrez Gene: APLP2 Amyloid beta (A4) precursor-like protein 2". CS1 maint: discouraged parameter (link) Leach R, Ko M, Krawetz ... "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 ...
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 ...
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. ...
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 ...
"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 ...
"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 ...
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. ...
... 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 ...
Alzheimer-type neuropathology in transgenic mice overexpressing V717F beta-amyloid precursor protein. Nature. February 1995, ... Roles of proteolysis and lipid rafts in the processing of the amyloid precursor protein and prion protein. Biochem. Soc. Trans ... Comparison of neurodegenerative pathology in transgenic mice overexpressing V717F beta-amyloid precursor protein and ... 1991年,學者提出類澱粉胜肽假說,認為β類澱粉胜肽(英语:Beta amyloid)(Aβ)在大腦堆積可能是
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. ...
"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 ...
"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 ...
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 ...
"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 ...
Enzymer reagerer med APP (amyloid-precursor-protein) og skærer det i fragmenter. Beta-amyloid-fragmentet er centralt i ... Alzheimer-type Neuropathology in Transgenic Mice Overexpressing V717F Beta-amyloid Precursor Protein. Nature. 1995;373(6514): ... Comparison of Neurodegenerative Pathology in Transgenic Mice Overexpressing V717F Beta-amyloid Precursor Protein and ... Roles of Proteolysis and Lipid Rafts in the Processing of the Amyloid Precursor Protein and Prion Protein. Biochemical Society ...
"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 ...
... 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 ...
"Familial Alzheimer's disease mutations inhibit gamma-secretase-mediated liberation of beta-amyloid precursor protein carboxy- ... The most well-known substrate of gamma secretase is amyloid precursor protein, a large integral membrane protein that, when ... complex with the γ-secretase activating protein facilitates the gamma cleavage of amyloid precursor protein into β-amyloid. The ... Zhang, H; Ma, Q; Zhang, YW; Xu, H (January 2012). "Proteolytic processing of Alzheimer's β-amyloid precursor protein". Journal ...
... 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 ... Svedružić Ž.M.; Odorčić I.; Chang C.H.; Svedružić D. (2020). "Substrate Channeling via a Transient Protein-Protein Complex: The ... Svedružić Ž.M.; Odorčić I.; Chang C.H.; Svedružić D. (2020). "Substrate Channeling via a Transient Protein-Protein Complex: The ...
... localization in human cerebral cortex and generation of amyloidogenic fragments from the beta-amyloid precursor protein". ... Cathepsin G is a protein that in humans is encoded by the CTSG gene. It is one of the three serine proteases of the ... Gabay JE, Scott RW, Campanelli D, Griffith J, Wilde C, Marra MN, Seeger M, Nathan CF (July 1989). "Antibiotic proteins of human ... Cathepsin G is a 255-amino-acid-residue protein including an 18-residue signal peptide, a two-residue activation peptide at the ...
2002). "The gamma-secretase-generated intracellular domain of beta-amyloid precursor protein binds Numb and inhibits Notch ... Numb-like protein is a protein that in humans is encoded by the NUMBL gene. NUMBL has been shown to interact with MAP3K7IP2. ... 2006). "A protein-protein interaction network for human inherited ataxias and disorders of Purkinje cell degeneration". Cell. ... a novel protein-protein interaction module". Genes Dev. 11 (17): 2239-49. doi:10.1101/gad.11.17.2239. PMC 275390. PMID 9303539 ...
"Lysosomal processing of amyloid precursor protein to A beta peptides: a distinct role for cathepsin S". The Biochemical Journal ... Protein Engineering. 11 (11): 1007-13. doi:10.1093/protein/11.11.1007. PMID 9876921. Söderström M, Salminen H, Glumoff V, ... Cathepsin S is a protein that in humans is encoded by the CTSS gene. Transcript variants utilizing alternative polyadenylation ... While lysosomal proteases terminally degrade proteins in lysosomes, cathepsin S has own distinctive physiological role. This ...
Presenile-dementia and cerebral- hemorrhage linked to a mutation at codon-692 of the beta-amyloid precursor protein gene. Nat ... Amyloid-beta transmission or unexamined bias? Nature. 2016;537(7620):E7-E8. Kavousi M, et al. Comparison of application of the ...
... of Amyloid-beta Precursor Protein Directs Human Embryonic Stem Cell Proliferation and Differentiation into Neuronal Precursor ... Neural precursor cells in the human SVZ are known to yield offspring which can then produce glial cells or even migrate and ... and extracellular matrix proteins (e.g. tenascin, CD34) have been linked to the mechanisms of neuropoiesis. Many of these ...
Alzheimer's disease is characterized by the buildup of amyloid precursor protein and subsequent beta-amyloid plaques in the ...
"Evolutionary origin of a Kunitz-type trypsin inhibitor domain inserted in the amyloid beta precursor protein of Alzheimer's ... Alzheimer's amyloid precursor protein (APP), and tissue factor pathway inhibitor (TFPI). Standalone Kunitz domains are used as ... a domain found in an alternatively spliced form of Alzheimer's amyloid beta-protein; domains at the C-termini of the alpha-1 ... They are short (about 50 to 60 amino acid residues) alpha/beta proteins with few secondary structures. The fold is constrained ...
"Transgenic tomatoes expressing human beta-amyloid for use as a vaccine against Alzheimer's disease". Biotechnology letters. 30 ... Kurstaki Insect Control Protein". Nature Biotechnology. 7 (12): 1265-1269. doi:10.1038/nbt1289-1265.. ... the precursor to ethylene. DNAP's tomato, called Endless Summer, inserted a truncated version of the ACC synthase gene into the ... "Fruit Cell Wall Proteins Help Fungus Turn Tomatoes From Ripe To Rotten". Science Daily. Jan 31, 2008. Retrieved 29 August 2010. ...
amyloid-beta formation. • amyloid precursor protein metabolic process. • neutrophil degranulation. • regulation of canonical ... from amyloid precursor protein (APP). Accumulation of amyloid beta is associated with the onset of Alzheimer's disease.[6] ... Selkoe DJ (1994). "Cell biology of the amyloid beta-protein precursor and the mechanism of Alzheimer's disease". Annu. Rev. ... Beta-amyloid production[edit]. Transgenic mice that over-expressed mutant presenilin-1 show an increase of beta-amyloid-42(43) ...
Studies suggest that neurotrophic factors have a protective role against amyloid beta toxicity.[85] ... positive regulation of non-membrane spanning protein tyrosine kinase activity. • transmembrane receptor protein tyrosine kinase ... in cortical precursors displaying EGFP-positive condensed apoptotic nuclei and a 2-4 fold increase in cortical precursors that ... Binding proteins: IGFBP (1, 2, 3, 4, 5, 6, 7). *Cleavage products/derivatives with unknown target: Glypromate (GPE, (1-3)IGF-1) ...
Hiltunen M, van Groen T, Jolkkonen J (2009). "Functional roles of amyloid-beta protein precursor and amyloid-beta peptides: ... "Beta-secretase cleavage of Alzheimer's amyloid precursor protein by the transmembrane aspartic protease BACE". Science 286 ( ... Shinkai Y, Yoshimura M, Ito Y, Odaka A, Suzuki N, Yanagisawa K, Ihara Y (September 1995). "Amyloid beta-proteins 1-40 and 1-42( ... Zou K, Gong JS, Yanagisawa K, Michikawa M (June 2002). "A novel function of monomeric amyloid beta-protein serving as an ...
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 ... including mutations to the amyloid precursor protein (APP) and presenilins 1 and 2 genes, and familial inheritance of ... combined with the observed increase in AD brains of BACE1-AS and corresponding increases in BACE1 protein and amyloid beta,[5] ...
This paper provided the first direct evidence that a fragment of the amyloid precursor protein could kill neurons, and helped ... 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. ... it was unclear whether amyloid beta was a byproduct of neuronal degeneration or a contributor to that degeneration. ...
positive regulation of protein localization to plasma membrane. • response to amyloid-beta. • cellular response to amyloid-beta ... negative regulation of amyloid precursor protein catabolic process. • ... protein binding. • identical protein binding. • copper ion binding. • lamin binding. • amyloid-beta binding. • protease binding ... PrPC protein is one of several cellular receptors of soluble amyloid beta (Aβ) oligomers, which are canonically implicated in ...
Studies suggest that neurotrophic factors have a protective role against amyloid beta toxicity.[84] ... positive regulation of non-membrane spanning protein tyrosine kinase activity. • transmembrane receptor protein tyrosine kinase ... Bartkowska K, Paquin A, Gauthier AS, Kaplan DR, Miller FD (December 2007). "Trk signaling regulates neural precursor cell ... Binding proteins: IGFBP (1, 2, 3, 4, 5, 6, 7). *Cleavage products/derivatives with unknown target: Glypromate (GPE, (1-3)IGF-1) ...
The protein is composed of alpha helices and beta sheets that form two domains.[8] The N- and C- terminal sequences are ... erythroid precursors in the bone marrow, it binds to it and is transported into the cell in a vesicle by receptor-mediated ... "Transferrin is an insulin-like growth factor-binding protein-3 binding protein". The Journal of Clinical Endocrinology and ... regulation of protein stability. • transferrin transport. • iron ion homeostasis. • platelet degranulation. • ion transport. • ...
amyloid precursor protein metabolic process. · neurotransmitter receptor biosynthetic process. · regulation of dendrite ... beta-amyloid binding. · acetylcholinesterase activity. · acetylcholinesterase activity. · carboxylesterase activity. · ... Pakaski M, Kasa P. Role of acetylcholinesterase inhibitors in the metabolism of amyloid precursor protein.. Current drug ... positive regulation of protein secretion. · regulation of axonogenesis. · regulation of synaptic transmission. · protein ...
... 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 ... protein kinase inhibitor activity. • protein binding. • kinesin binding. • protein kinase binding. • JUN kinase binding. • ... "Entrez Gene: MAPK8IP1 mitogen-activated protein kinase 8 interacting protein 1".. *^ a b c d e f Yasuda, J; Whitmarsh A J; ...
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 ... protein binding. • protein heterodimerization activity. • acid-amino acid ligase activity. • NEDD8 activating enzyme activity. ...
"islet amyloid polypeptide precursor [Homo sapiens]". NCBI.. (the current NCBI RefSeq) *^ a b Roberts AN, Leighton B, Todd JA, ... Proisletni amiloidni polipeptid (proIAPP, proamilin, proislet protein) proizvodi se u beta ćelijama (β-ćelijama) gušterače kao ... "Intracellular amyloid-like deposits contain unprocessed pro-islet amyloid polypeptide (proIAPP) in beta cells of transgenic ... Paulsson JF, Westermark GT (July 2005). "Aberrant processing of human proislet amyloid polypeptide results in increased amyloid ...
cellular response to amyloid-beta. • positive regulation of vascular smooth muscle cell proliferation. • negative regulation of ... protein stabilization. • myotube cell development. • positive regulation of DNA replication. • myoblast proliferation. • ... "Sequence of cDNA encoding human insulin-like growth factor I precursor". Nature. 306 (5943): 609-11. PMID 6358902. doi:10.1038/ ... protein kinase B signaling. • regulation of multicellular organism growth. • positive regulation of cell migration. • platelet ...
Studies in cells and in mouse have shown that specifically targeting Amyloid beta-producing genes (e.g. BACE1 and APP) by RNAi ... In fission yeast this complex contains argonaute, a chromodomain protein Chp1, and a protein called Tas3 of unknown function.[ ... Another effort decreased the precursors of likely carcinogens in tobacco plants.[178] Other plant traits that have been ... This ancestral RNAi system probably contained at least one dicer-like protein, one argonaute, one PIWI protein, and an RNA- ...
Other/ungrouped: Amyloid precursor protein secretase *Alpha secretase. *Beta-secretase 1. *Beta-secretase 2 ... Human proteins containing this domain[edit]. BACE1; BACE2; CTSD; CTSE; NAPSA; PGA5; PGC; REN; ... Hartsuck JA, Koelsch G, Remington SJ (May 1992). "The high-resolution crystal structure of porcine pepsinogen". Proteins. 13 (1 ... they tend to cleave dipeptide bonds that have hydrophobic residues as well as a beta-methylene group. Unlike serine or cysteine ...
Through translational processing, insulin is encoded as a 110 amino acid precursor but is secreted as a 51 amino acid protein.[ ... Amylin, also known as islet amyloid polypeptide (IAPP).[17] The function of amylin is to slow the rate of glucose entering the ... Beta cells (β cells) are a type of cell found in pancreatic islets that synthesize and secrete insulin and amylin. Beta cells ... Research has shown that beta cells can be differentiated from human pancreas progenitor cells.[31] These differentiated beta ...
"Alzheimer-type neuropathology in transgenic mice overexpressing V717F beta-amyloid precursor protein". Nature 373 (6514): 523- ... "Roles of proteolysis and lipid rafts in the processing of the amyloid precursor protein and prion protein". Biochem. Soc. Trans ... "Comparison of neurodegenerative pathology in transgenic mice overexpressing V717F beta-amyloid precursor protein and ... Lauren J, Gimbel D, et al. (Februari 2009). "Cellular prion protein mediates impairment of synaptic plasticity by amyloid-beta ...
Mosselman S, Höppener JW, Lips CJ, Jansz HS (1989). "The complete islet amyloid polypeptide precursor is encoded by two exons ... Timus: Timozin (Timozin α1, Timozin beta) • Timopoietin • Timulin Organi za varenje: Želudac: gastrin • grelin • Duodenum: CCK ... "A novel peptide in the calcitonin gene related peptide family as an amyloid fibril protein in the endocrine pancreas". Biochem ... "Amyloid fibrils in human insulinoma and islets of Langerhans of the diabetic cat are derived from a neuropeptide-like protein ...
Other/ungrouped: Amyloid precursor protein secretase *Alpha secretase. *Beta-secretase 1. *Beta-secretase 2 ... This 20-S protein is composed of 28 subunits arranged in four rings of seven. ... "Contribution of proteasomal beta-subunits to the cleavage of peptide substrates analyzed with yeast mutants". The Journal of ...
G-CSF has been shown to reduce inflammation, reduce amyloid beta burden, and reverse cognitive impairment in a mouse model of ... mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signal transduction ... The G-CSF-receptor is present on precursor cells in the bone marrow, and, in response to stimulation by G-CSF, initiates ... positive regulation of protein kinase B signaling. • positive regulation of actin filament polymerization. • cellular response ...
"Processing of the pre-beta-amyloid protein by cathepsin D is enhanced by a familial Alzheimer's disease mutation". European ... The main function of cathepsin D is to degrade proteins and activate precursors of bioactive proteins in pre-lysosomal ... macrophage inflammatory protein-1 beta, and SLC that are expressed in human breast cancer". The American Journal of Pathology. ... both produced from a single protein precursor. Cathepsin D is an aspartic endo-protease that is ubiquitously distributed in ...
Beta-amyloid is a small piece of a larger protein called the amyloid precursor protein (APP). Once APP is activated, it is cut ... Mutations to the amyloid beta A4 precursor protein (APP) located on the long arm of chromosome 21 (21q21.3) cause familial ... "Increased β-amyloid release and levels of amyloid precursor protein (APP) in fibroblast cell lines from family members with the ... suggesting that the Asn141Ile mutation alters amyloid precursor protein (APP) metabolism causing an increased rate of protein ...
... since the latter can irreversibly transform from its native alpha-helical structure to beta-sheet aggregates and form amyloid ... Keller A, Eistetter HR, Voss T, Schafer KP (Aug 1991). "The pulmonary surfactant protein C (SP-C) precursor is a type II ... Surfactant protein C (SP-C), is one of the pulmonary surfactant proteins. In humans this is encoded by the SFTPC gene. It is a ... "Lipid-protein interactions of hydrophobic proteins SP-B and SP-C in lung surfactant assembly and dynamics". Pediatric pathology ...
Beta-amyloid Beta-amyloid(Aβ) (also called 'amyloid beta') plaques start with a protein called amyloid precursor protein (APP ... The beta-amyloid bundles (plaque) are made up of pieces of beta-amyloid protein that were once part of a healthy neuron. These ... which are made mostly from another protein called beta-amyloid, they are also sometimes called beta-amyloid bundles or 'bundles ... have biomarker evidence of amyloid beta (Aβ) build-up in the brain. This amyloid beta (Aβ) is linked to changes in the ...
... called amyloid beta (Aβ). Aβ is a fragment from the larger amyloid precursor protein (APP). APP is a transmembrane protein that ... Enzymes act on the APP (amyloid precursor protein) and cut it into fragments. The beta-amyloid fragment is crucial in the ... In early 2017, a trial of verubecestat, which inhibits the beta-secretase protein responsible for creating beta-amyloid protein ... suggesting that a close relative of the beta-amyloid protein, and not necessarily the beta-amyloid itself, may be a major ...
Alzheimer-type Neuropathology in Transgenic Mice Overexpressing V717F Beta-amyloid Precursor Protein». Nature. 373 (6514): 523- ... Hooper NM (2005). «Roles of Proteolysis and Lipid Rafts in the Processing of the Amyloid Precursor Protein and Prion Protein». ... Comparison of Neurodegenerative Pathology in Transgenic Mice Overexpressing V717F Beta-amyloid Precursor Protein and ... Turner PR, O'Connor K, Tate WP, Abraham WC (2003). «Roles of Amyloid Precursor Protein and its Fragments in Regulating Neural ...
The misfolding of the protein causes it to have insoluble beta-pleated sheets,[3] creating an amyloid. Amyloid, the aggregation ... Protein precursors include immunoglobulin-derived light chains and transthyretin mutations.[2] ... Amyloid, a misfolded and insoluble protein, can become a deposit in the heart's atria, valves, or ventricles. These deposits ... Cardiac amyloidosis is a subcategory of amyloidosis where there is the depositing of the protein amyloid in the cardiac muscle ...
Other/ungrouped: Amyloid precursor protein secretase *Alpha secretase. *Beta-secretase 1. *Beta-secretase 2 ... identical protein binding. • peptidase activity. • hydrolase activity. • virus receptor activity. • protein homodimerization ... The protein encoded by the DPP4 gene is an antigenic enzyme expressed on the surface of most cell types and is associated with ... protein binding. • serine-type endopeptidase activity. Cellular component. • lamellipodium membrane. • extracellular exosome. • ...
"Mutation of the beta-amyloid precursor protein in familial Alzheimers 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 ...
beta/A4 amyloid is derived from the amyloid precursor protein (APP), an integral membrane protein that exists as three major ... Protein phosphorylation regulates secretion of Alzheimer beta/A4 amyloid precursor protein. G L Caporaso, S E Gandy, J D ... Protein phosphorylation regulates secretion of Alzheimer beta/A4 amyloid precursor protein. G L Caporaso, S E Gandy, J D ... Protein phosphorylation regulates secretion of Alzheimer beta/A4 amyloid precursor protein. G L Caporaso, S E Gandy, J D ...
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 ...
APBB2 amyloid beta precursor protein binding family B member 2 [Homo sapiens] APBB2 amyloid beta precursor protein binding ... The protein encoded by this gene interacts with the cytoplasmic domains of amyloid beta (A4) precursor protein and amyloid beta ... General protein information Go to the top of the page Help Preferred Names. amyloid-beta A4 precursor protein-binding family B ... mRNA and Protein(s) * NM_001166050.1 → NP_001159522.1 amyloid-beta A4 precursor protein-binding family B member 2 isoform b ...
Beta-amyloid precursor protein staining of nonaccidental central nervous system injury in pediatric autopsies.. Reichard RR1, ... Immunohistochemical staining for beta-amyloid precursor protein (betaAPP) is a well-established marker of traumatic axonal ...
The beta-amyloid precursor protein (betaAPP) is a transmembrane protein that is exclusively phosphorylated on serine residues ... Ectodomain phosphorylation of beta-amyloid precursor protein at two distinct cellular locations.. Walter J., Capell A., Hung A. ... APPssw-beta). This antibody previously established the cellular location of the beta-secretase cleavage of Swedish betaAPP as a ... European Bioinformatics InstituteProtein Information ResourceSIB Swiss Institute of Bioinformatics. UniProt is an ELIXIR core ...
AD brains contain numerous amyloid plaques surrounded by dystrophic neurites, and show profound synaptic loss, neurofibrillary ... The amyloid plaques are composed of amyloid beta-peptide (A beta), a 40-42-amino-acid fragment of the beta-amyloid precursor ... Alzheimer-type neuropathology in transgenic mice overexpressing V717F beta-amyloid precursor protein Nature. 1995 Feb 9;373( ... Amyloid beta-Peptides / metabolism* * Amyloid beta-Protein Precursor / genetics * Amyloid beta-Protein Precursor / metabolism ...
apl-1, a Caenorhabditis elegans gene encoding a protein related to the human beta-amyloid protein precursor. I Daigle and C Li ... apl-1, a Caenorhabditis elegans gene encoding a protein related to the human beta-amyloid protein precursor ... apl-1, a Caenorhabditis elegans gene encoding a protein related to the human beta-amyloid protein precursor ... apl-1, a Caenorhabditis elegans gene encoding a protein related to the human beta-amyloid protein precursor ...
X11L2, a new member of the X11 protein family, interacts with Alzheimers beta-amyloid precursor protein. Tanahashi, H., Tabira ... We screened proteins for interaction with Alzheimers beta-amyloid precursor protein (APP) and cloned a new member of the X11 ... Synonyms: Adapter protein X11gamma, Amyloid beta A4 precursor protein-binding family A member 3, MGC:15815, MINT3, Mint-3, ... ... a third member of the X11 protein family interacting with Alzheimers beta-amyloid precursor protein. Tanahashi, H., Tabira, T ...
Amyloid beta protein toxicity mediated by the formation of amyloid-beta protein precursor complexes. Lu, D.C., Shaked, G.M., ... The amyloid beta-protein precursor (APP) is proteolytically cleaved to generate the amyloid beta-protein (Abeta), the principal ... In vivo, the levels of soluble amyloid beta protein correlated with caspase-cleaved fragments of the amyloid precursor protein ... Caspase cleavage of the amyloid precursor protein modulates amyloid beta-protein toxicity. Lu, D.C., Soriano, S., Bredesen, D.E ...
A beta) is an invariant feature of Alzheimers disease which precedes symptoms of dementia by years or decades. The only ... Progressive cerebral deposition of the 39-43-amino-acid amyloid beta-protein ( ... Mutation of the beta-amyloid precursor protein in familial Alzheimers disease increases beta-protein production Nature. 1992 ... disease which have been identified so far are missense mutations in the gene encoding the beta-amyloid precursor protein (beta- ...
Compare amyloid beta precursor protein binding family A member 2 ELISA Kits from leading suppliers on Biocompare. View ... amyloid beta precursor protein binding family A member 2 ELISA Kits. Clear ... amyloid beta precursor protein binding family A member 2 ELISA Kits. The ELISA (enzyme-linked immunosorbent assay) is a well- ... Bovine Amyloid beta A4 precursor protein-binding family A member 2 (APBA2) ELISA Kit ...
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Adapter protein that forms a transcriptionally active complex with the gamma-secretase-derived amyloid precursor protein (APP) ... Protein. Similar proteins. Species. Score. Length. Source. P46933. Amyloid-beta A4 precursor protein-binding family B member 1 ... "Regulation of beta-amyloid secretion by FE65, an amyloid protein precursor-binding protein.". Sabo S.L., Lanier L.M., Ikin A.F. ... "Regulation of beta-amyloid secretion by FE65, an amyloid protein precursor-binding protein.". Sabo S.L., Lanier L.M., Ikin A.F. ...
... amyloid beta precursor protein binding family A member 2), Authors: Dessen P. Published in: Atlas Genet Cytogenet Oncol ... amyloid beta (A4) precursor protein-binding, family A, member 2 (X11-like). ... amyloid-beta binding in utero embryonic development protein binding cytoplasm plasma membrane chemical synaptic transmission ... amyloid-beta binding in utero embryonic development protein binding cytoplasm plasma membrane chemical synaptic transmission ...
8-Tetrahydropyran-2-yl chromans: highly selective beta-site amyloid precursor protein cleaving enzyme 1 (BACE1) inhibitors. * ... 8-Tetrahydropyran-2-yl Chromans: Highly Selective Beta-Site Amyloid Precursor Protein Cleaving Enzyme 1 (BACE1) Inhibitors.. ... Beta-secretase 1. A. 406. Homo sapiens. Mutation(s): 0 Gene Names: BACE1, BACE, KIAA1149. EC: 3.4.23.46. ...
We perform a single molecule level study of the RERMS sequence of amyloid $\beta $/A4 precursor protein fragment on a clean Ag( ... Abstract: D10.00003 : Single Molecule Manipulation and Self-Assembly of Amyloid $\beta $/A4 Precursor Protein on Ag(111)*. 3:18 ... Moreover, we are able to form a well ordered two-dimensional layer of the protein fragment by increasing the deposition time. A ... The mechanical stability of individual protein fragments are checked by laterally manipulating them with the STM tip. ...
... beta] Precursor Protein/Presenilin 2 Mouse Model of Alzheimers Disease.(Research Article) by International Journal of ... Early Contextual Fear Memory Deficits in a Double-Transgenic Amyloid-[ ... MLA style: "Early Contextual Fear Memory Deficits in a Double-Transgenic Amyloid-[beta] Precursor Protein/Presenilin 2 Mouse ... APA style: Early Contextual Fear Memory Deficits in a Double-Transgenic Amyloid-[beta] Precursor Protein/Presenilin 2 Mouse ...
Powerful beneficial effects of benfotiamine on cognitive impairment and beta-amyloid deposition in amyloid precursor protein/ ... Powerful beneficial effects of benfotiamine on cognitive impairment and beta-amyloid deposition in amyloid precursor protein/ ... "Powerful Beneficial Effects of Benfotiamine On Cognitive Impairment and Beta-amyloid Deposition in Amyloid Precursor Protein/ ... Powerful beneficial effects of benfotiamine on cognitive impairment and beta-amyloid deposition in amyloid precursor protein/ ...
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Amyloid beta a4 precursor protein-binding family B member 1 (FE65) interactomics revealed synaptic vesicle glycoprotein 2A ( ... Amyloid beta a4 precursor protein-binding family B member 1 (FE65) interactomics revealed synaptic vesicle glycoprotein 2A ( ... Amyloid beta a4 precursor protein-binding family B member 1 (FE65) interactomics revealed synaptic vesicle glycoprotein 2A ( ... SV2A) and sarcoplasmic/endoplasmic reticulum calcium ATPase 2 (SERCA2) as new binding proteins in the human brain. Mol Cell ...
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Retinal Amyloid Precursor Protein (APP) processing and amyloid-beta (Aβ) transport in an Alzheimers disease (AD) mouse model ... Retinal Amyloid Precursor Protein (APP) processing and amyloid-beta (Aβ) transport in an Alzheimers disease (AD) mouse model ... Retinal Amyloid Precursor Protein (APP) processing and amyloid-beta (Aβ) transport in an Alzheimers disease (AD) mouse model. ... Results : AD mice retinas exhibited enhanced APP production with increased amyloid processing and Aβ accumulation vs. wt mice. ...
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  • Extracellular deposition of the beta/A4 amyloid peptide is a characteristic feature of the brain in patients with Alzheimer disease. (pnas.org)
  • Sequential cleavage by beta-secretase 1 (BACE) and gamma-secretase (γ-secretase) produces the amyloid-beta peptide fragment that aggregates into clumps called amyloid plaques in the brains affected by Alzheimer's disease. (wikipedia.org)
  • The amyloid plaques are composed of amyloid beta-peptide (A beta), a 40-42-amino-acid fragment of the beta-amyloid precursor protein (APP). (nih.gov)
  • The major component of senile plaques found in the brains of Alzheimer disease patients is the beta-amyloid peptide, which is derived from a larger amyloid precursor protein (APP). (pnas.org)
  • Similar to the Drosophila, human, and mouse APP-related proteins, APL-1 does not appear to contain the beta-amyloid peptide. (pnas.org)
  • At APP695 subtype, with the majority of membrane proteins, transmembrane proteins of the orphan receptor characteristics, it is easier by complex protein hydrolysis pathway cracking of varying sizes peptide fragments, including a relatively long extracellular amino terminal peptide fragment, the smaller the A beta protein (the main component of senile plaques) and a variety of sizes ranging from APP intracellular domain (AICD). (biology-online.org)
  • It cleaves at the N-terminus of the A-beta peptide sequence of APP. (researchandmarkets.com)
  • The 31-amino acid peptide results from the proteolytic cleavage of the C- terminus of beta-amyloid precursor protein (APP) at Asp 739 -Ala 740 by caspases. (rpeptide.com)
  • Alzheimer's disease (AD) is a neurodegenerative disorder characterized by abnormal deposition of neurotoxic amyloid-β (Aβ) peptide. (diva-portal.org)
  • In this article we provide evidence that amyloid beta-peptide (A beta), the substance which accumulates in AD plaques, exacerbates excitotoxic and metabolic compromises to neurons resulting in changes in the cytoskeleton which resemble those seen in the neurofibrillary tangles of AD. (elsevier.com)
  • A beta peptide immunization reduces behavioural impairment and plaques in a model of Alzheimer's disease. (moldiag.com)
  • A beta peptide vaccination prevents memory loss in an animal model of Alzheimer's disease. (moldiag.com)
  • Overexpression of APP mRNAs is therefore an unlikely explanation for the deposition of the beta-amyloid (beta/A4) peptide in FAD brains. (ox.ac.uk)
  • Amyloid plaques, composed mainly of the 39-43 amino acid βA4 peptide, are a characteristic feature of Alzheimer's disease. (jneurosci.org)
  • Formation of senile plaques containing the beta-amyloid peptide (A beta) derived from the amyloid precursor protein (APP) is an invariant feature of Alzheimer's disease (AD). (uni-muenchen.de)
  • Aim of this study was to compare levels of different CSF biomarkers, including total secreted β-amyloid precursor protein (sAPP), sAPP-alpha form (sAPPα), amyloid-beta (Aβ) peptide, total-tau protein and hyperphosphorylated-tau protein in subjects from NPH and Non-NPH Control (NNC). (elsevier.com)
  • ELISA was used separately to determine levels of sAPPα, Aβ peptide, total-tau and phospho-tau proteins. (elsevier.com)
  • β-Amyloid Peptide: the Cell Compartment Multi-faceted Interaction in Alzheimer's Disease. (alzforum.org)
  • Amyloid-β peptide (Aβ) is believed to play a central role in the pathogenesis of Alzheimer's disease. (jneurosci.org)
  • These hAbeta-loxP-KI mice express mouse APP protein with a "humanized" amyloid beta peptide sequence. (jax.org)
  • 4 Amyloid Beta ( Aβ) is formed through cleavage of the APP, generating a peptide 36-43 amino acids long. (google.com)
  • This disease is characterized by intraneuronal tangles and extracellular plaques, and the amyloid beta-peptide (Aβ), which is derived from APP upon cleavage by β- and γ-secretases, is the major component of the plaques. (biologists.org)
  • The simulation: fibrils are thought to be symmetric assemblies, which means that they are formed by stacking together many identical copies of a protein or peptide. (bakerlab.org)
  • The amyloid precursor protein may be processed by several different pathways, one of which produces the amyloid beta-peptide betaA4 present in the amyloid plaques characteristic of Alzheimer's disease. (lancs.ac.uk)
  • Synthetic β-amyloid peptide, conjugated to KLH. (sigmaaldrich.com)
  • Reacts with beta-amyloid peptide and secreted amyloid precursor protein (alpha-secretase cleaved). (abcam.com)
  • It does however strongly recognize alpha-secretase cleaved soluble APP as well as b-amyloid peptide (40 and 42), in both cases native an denatured forms. (abcam.com)
  • Synthetic peptide corresponding to Human Amyloid Precursor Protein aa 672-689 conjugated to keyhole limpet haemocyanin. (abcam.com)
  • Ab12266 recognizes an epitope within amino acids 1-17 of the amyloid beta/A4 peptide region of APP. (abcam.com)
  • As such it recognises the C-terminus of alpha-secretase cleaved APP and amyloid beta/A4 peptide. (abcam.com)
  • 4. The method of claim 1 wherein said amyloid precursor protein (APP) substrate comprises a synthetic peptide. (google.com.au)
  • Alzheimer's disease (AD) is characterized by the accumulation of β-amyloid peptide (Aβ) in the brain because of an imbalance between Aβ production and clearance. (nature.com)
  • Expression of amyloid β peptides in APP-PS1-HEK293 cells was lower in ICT-treated groups compared with that in the control group. (peerj.com)
  • Amyloid-β peptides (AβPs) are generated through sequential cleavage of amyloid precursor protein (APP) by beta-site amyloid cleaving enzyme (BACE)1 and γ-secretase (presenilin-1 (PS1)), which play pivotal roles in AD pathogenesis ( Querfurth & LaFerla, 2010 ). (peerj.com)
  • Although amyloid precursor protein (APP) due to the cytotoxicity of A beta peptides, has been intensively studied, the physiological role of APP still remains wrapped up in veil. (ucf.edu)
  • The plaques are primarily composed of aggregated amyloid beta (Abeta) peptides . (bvsalud.org)
  • Amyloid beta (Abeta) peptides are hypothesized to cause the initiation and progression of AD based on pathologic data from AD patients, genetic analysis of mutations that cause early onset forms of AD, and preclinical studies. (geoscience.net)
  • Amyloid beta (Aβ) peptides are related to the pathogenesis of Alzheimer's disease (AD). (houstonmethodist.org)
  • The search for therapeutic strategies that lower these peptides has mainly focused on the proteolytic processing of the (3-amyloid precursor protein (APP), and other post-transcriptional pathways. (houstonmethodist.org)
  • While some opinion holds that amyloid plaques are a late stage by-product of the disease process, the consensus view is that amyloid plaques and/or soluble aggregates of amyloid peptides are more likely to be intimately, and perhaps causally, involved in Alzheimer's disease. (justia.com)
  • Aggregation and accumulation of amyloid-β (Aβ) peptides in the CNS is thought to underlie most cases of Alzheimer's disease ( Haass and Selkoe, 2007 ). (jneurosci.org)
  • The β-amyloid precursor protein (APP) is cleaved sequentially by the proteolytic enzymes β-and γ-secretase to produce β-amyloid (Aβ) peptides with the Aβ1-42 and the Aβ1-40 forms being the most prevalent. (sigmaaldrich.com)
  • It is characterized by progressive accumulation of aggregated amyloid β (Aβ) peptides and hyperphosphorylated Tau protein, memory decline, and neurodegeneration. (nature.com)
  • These are subsequently cleaved by γ-secretase at multiple sites in the transmembrane region, releasing small peptides, Aβ 1-40 and Aβ 1-42 , the major components of AD-associated amyloid fibrils. (biologists.org)
  • One of the major histopathological hallmarks of Alzheimer's disease (AD) is redundant senile plaques mainly composed of beta-amyloid (Abeta) aggregates. (lu.se)
  • Alternative cleavage of the amyloid precursor protein (APP), occurring in both normal and AD subjects, results in the generation and secretion of soluble APP (sAPP) and Abeta. (lu.se)
  • Neither the levels of CSF-beta-sAPP nor CSF-Abeta(42) differed when comparing ApoE4 allele-positive with allele-negative individuals. (lu.se)
  • Zinc released from excited glutamatergic neurons accelerates amyloid beta (Abeta) aggregation, underscoring the therapeutic potential of zinc chelation for the treatment of Alzheimer's disease (AD). (yonsei.ac.kr)
  • In order to elucidate the possible role of zinc influx in secretase-processed Abeta production, SH-SY5Y cells stably expressing amyloid precursor protein (APP) were treated with pyrrolidine dithiocarbamate (PDTC), a zinc ionophore, and the resultant changes in APP processing were examined. (yonsei.ac.kr)
  • Progressive cerebral deposition of the amyloid beta-protein (Abeta) is believed to play a pivotal role in the pathogenesis of Alzheimer's disease (AD). (qxmd.com)
  • Mutations in two familial AD-linked genes, presenilins 1 (PS1) and 2 (PS2), selectively increase the production of Abeta42 in cultured cells and the brains of transgenic mice, and gene deletion of PS1 shows that it is required for normal gamma-secretase cleavage of the beta-amyloid precursor protein (APP) to generate Abeta. (qxmd.com)
  • Based on this hypothesis, beta-site amyloid precursor protein (APP)-cleaving enzyme 1 (BACE1) inhibitors are an attractive therapeutic approach for AD because cleavage of the APP by BACE1 is required to form Abeta. (geoscience.net)
  • The App-201 isoform (695 aa protein) is encoded by 16 exons, of which the Abeta sequence is encoded by exon 14. (jax.org)
  • The App-206 isoform (770 aa protein) is encoded by 18 exons, of which the Abeta sequence is encoded by exon 16. (jax.org)
  • Mouse monoclonal anti-ABETA was used to treat old WT PDAPP mice with amyloid accumulation and learning deficits in an attempt to improve learning and decrease accumulation, however no response was observed. (sigmaaldrich.com)
  • Systemic administration of anti-amyloid-beta (Abeta) antibodies results in reduced parenchymal amyloid but increased vascular amyloid and microhemorrhage in amyloid precursor protein (APP) transgenic mice. (unboundmedicine.com)
  • Deglycosylated anti-Abeta antibodies may be preferable to unmodified IgG because they retain the cognition-enhancing and amyloid-reducing properties of anti-Abeta immunotherapy, while greatly attenuating the increased vascular amyloid deposition and microhemorrhage observed with unmodified IgG. (unboundmedicine.com)
  • It is coded for by the gene APP and is best known as the precursor molecule whose proteolysis generates amyloid beta (Aβ), a polypeptide containing 37 to 49 amino acid residues, whose amyloid fibrillar form is the primary component of amyloid plaques found in the brains of Alzheimer's disease patients. (wikipedia.org)
  • The protein encoded by this gene interacts with the cytoplasmic domains of amyloid beta (A4) precursor protein and amyloid beta (A4) precursor-like protein 2. (nih.gov)
  • We have isolated several cDNAs encoding an APP-related protein in the nematode Caenorhabditis elegans and have designated the corresponding gene as apl-1. (pnas.org)
  • Because APP-related proteins seem to be conserved through evolution, the apl-1 gene from C. elegans should be important for determining the normal function of human APP. (pnas.org)
  • Genomic organization of the human X11L2 gene (APBA3), a third member of the X11 protein family interacting with Alzheimer's beta-amyloid precursor protein. (wikigenes.org)
  • The only specific molecular defects that cause Alzheimer's disease which have been identified so far are missense mutations in the gene encoding the beta-amyloid precursor protein (beta-APP) in certain families with an autosomal dominant form of the disease (familial Alzheimer's disease, or FAD). (nih.gov)
  • The APP gene encodes a membrane protein whose cleavage products serve various functions. (moldiag.com)
  • The amyloid beta-protein precursor (APP) gene and its products are implicated in the pathogenesis of Alzheimer's disease. (ox.ac.uk)
  • The protein encoded by this gene is a member of the X11 protein family. (nih.gov)
  • APPBP2 (Amyloid Beta Precursor Protein Binding Protein 2) is a Protein Coding gene. (genecards.org)
  • In humans, this protein is encoded by the gene AAAS. (biocompare.com)
  • APBB1 (Amyloid Beta Precursor Protein Binding Family B Member 1) is a Protein Coding gene. (genecards.org)
  • Abnormalities in gene regulation of the β-amyloid precursor protein ( βAPP) might be an important factor in the neuropathology of Alzheimer's disease. (elsevier.com)
  • Lahiri, D & Nall, C 1995, ' Promoter activity of the gene encoding the beta-amyloid precursor protein is up-regulated by growth factors, phorbol ester, retinoic acid and interleukin-1 ', Molecular Brain Research , vol. 32, no. 2, pp. 233-240. (elsevier.com)
  • this can happen when there is a mutation in one of the genes that creates a functional, but malformed, protein instead of the ineffective gene products that usually result from mutations. (wikipedia.org)
  • This "humanized" App knock-in strain, in which 3 point mutations were introduced into exon 14 of the mouse App gene, produces a mutant protein that is expected to more readily aggregate. (jax.org)
  • No App gene product (mRNA or protein) is detected. (jax.org)
  • β-amyloid gene is located on human chromosome 21q21. (sigmaaldrich.com)
  • β-amyloid gene acts as the substrate of insulin-degrading enzyme (IDE). (sigmaaldrich.com)
  • Familial AD (FAD), on the other hand, is associated with mutations in amyloid precursor protein (APP) on chromosome 21, apolipoprotein E gene on chromosome 19, presenilin-1 (PS1) on chromosome 14 (14q24.3) and presenilin-2 (PS2) on chromosome 1. (biologists.org)
  • Differential processing of amyloid-beta precursor protein directs human embryonic stem cell proliferation and differentiation into neuronal precursor cells. (nih.gov)
  • Addgene: A critical function for beta-amyloid precursor protein in neuronal migration revealed by in utero RNA interference. (addgene.org)
  • Recent findings concerning the normal function of beta APP and the mechanism of A beta toxicity place beta APP at the center of changes leading to neuronal degeneration in AD. (elsevier.com)
  • Detection of beta-A4 amyloid and its precursor protein in the muscle of a patient with juvenile neuronal ceroid lipofuscinosis (Spielmeyer-Vogt-Sjögren). (naver.com)
  • Mechanisms of action of amyloid-beta and its precursor protein in neuronal cell death. (alzforum.org)
  • Amyloid Beta is a derivative of the Amyloid Precursor Protein (APP), which is a protein that is believed to modulate neuronal excitability, synaptic plasticity, synaptogenesis, and neurite outgrowth. (google.com)
  • Early Contextual Fear Memory Deficits in a Double-Transgenic Amyloid-[beta] Precursor Protein/Presenilin 2 Mouse Model of Alzheimer's Disease. (thefreelibrary.com)
  • Here, we tested the effect of benfotiamine, a thiamine derivative with better bioavailability than thiamine, on cognitive impairment and pathology alterations in a mouse model of Alzheimer's disease, the amyloid precursor protein/presenilin-1 transgenic mouse. (unboundmedicine.com)
  • However, Gouras et al in patients with mild cognitive impairment (MCI) hippocampus and entorhinal cortex region of neurons found in A beta accumulation, and Mori and also with Down syndrome (Down syndrome ) in patients with brain tissue similar change. (biology-online.org)
  • However in Alzheimer's there was a greater accumulation of these proteins suggesting a pathologic role for them in this disease. (arvojournals.org)
  • AD mice retinas exhibited enhanced APP production with increased amyloid processing and Aβ accumulation vs. wt mice. (arvojournals.org)
  • Because of increased accumulation of AbetaPP in neurons after OA treatment , more AbetaPP turns to be cleaved by beta-secretase , producing neurotoxic betaCTF. (bvsalud.org)
  • β-amyloid is "stickier" than any other fragment produced from cut-up APP and due to this property it starts an accumulation process in the brain. (wikipedia.org)
  • Drugmakers have thought that BACE1 inhibitors could prevent the accumulation of amyloid plaque and slow the progression of Alzheimer's disease. (yahoo.com)
  • Pathological hallmarks of AD include the accumulation of β-amyloid in plaques and hyperphosphorylated tau in neurofibrillary tangles. (frontiersin.org)
  • Extracellular accumulation of Aβ leads to the formation of aggregates, fibrils and eventually amyloid deposits called neuritic plaques, which is the hallmark of Alzheimer′s disease (AD). (sigmaaldrich.com)
  • alpha secretase and beta secretase both remove nearly the entire extracellular domain to release membrane-anchored carboxy-terminal fragments that may be associated with apoptosis. (wikipedia.org)
  • BACE is a transmembrane protein with an extracellular aspartic acid protease domain. (wikipedia.org)
  • Although BACE cleaves the extracellular domains of several transmembrane proteins, its physiological function remains unknown. (wikipedia.org)
  • Animals transgenic for APP have previously failed to show extensive AD-type neuropathology, but we now report the production of transgenic mice that express high levels of human mutant APP (with valine at residue 717 substituted by phenylalanine) and which progressively develop many of the pathological hallmarks of AD, including numerous extracellular thioflavin S-positive A beta deposits, neuritic plaques, synaptic loss, astrocytosis and microgliosis. (nih.gov)
  • Cutting followed by the β and γ-secretase enzyme, resulting in extracellular s APP beta, A beta (A beta 40 and A beta 42) fragment and APP intracellular domain fragment. (biology-online.org)
  • The traditional view is that the extracellular A-beta deposition play an important role in the pathogenesis of Alzheimer's disease. (biology-online.org)
  • Tips, intracellular A beta aggregation before extracellular A beta deposition in Alzheimer's disease process. (biology-online.org)
  • This 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. (researchandmarkets.com)
  • This study focused on the role of extracellular ASN (eASN) in regulation of transcription of sirtuins (Sirts) and DNA-bound poly(ADP-ribose) polymerases (PARPs) - proteins crucial for cells' survival/death. (springer.com)
  • In the CNS, zinc occurs in two forms: the first being tightly bound to proteins and, secondly, the free, cytoplasmic, or extracellular form found in presynaptic vesicles. (frontiersin.org)
  • APP is a ubiquitous membrane protein that is physiologically processed by site-specific proteolysis firstly by α- or β-secretases, releasing a large fragment called APP S that contains most of the extracellular sequences of APP, a small extracellular stub, the transmembrane region and the cytoplasmic tail of APP (`AICD'-APP intracellular domain). (biologists.org)
  • Mutations in critical regions of amyloid precursor protein, including the region that generates amyloid beta (Aβ), cause familial susceptibility to Alzheimer's disease. (wikipedia.org)
  • Progressive cerebral deposition of the 39-43-amino-acid amyloid beta-protein (A beta) is an invariant feature of Alzheimer's disease which precedes symptoms of dementia by years or decades. (nih.gov)
  • Further, they confirm the relevance of the continuous A beta production by cultured cells for elucidating the fundamental mechanism of Alzheimer's disease. (nih.gov)
  • This shows that A beta may also accumulate in cells and play an important role in the early onset of Alzheimer's disease. (biology-online.org)
  • Therefore, in the animal Alzheimer's disease model, benfotiamine appears to improve the cognitive function and reduce amyloid deposition via thiamine-independent mechanisms, which are likely to include the suppression of glycogen synthase kinase-3 activities. (unboundmedicine.com)
  • The receptor for advanced glycation end products (RAGE) and amyloid-beta have both been implicated in the pathogenesis of Alzheimer's disease (AD) in brain. (arvojournals.org)
  • The beta-amyloid precursor protein is a cell surface protein with signal-transducing properties, and it is thought to play a role in the pathogenesis of Alzheimer's disease. (biomol.com)
  • Amyloid beta-protein (A beta), the principal constituent of senile plaques seen in Alzheimer's disease (AD), is derived by proteolysis from the beta-amyloid precursor protein (beta PP). The mechanism of A beta production in neurons, which are hypothesized to be a rich source of A beta in brain, remains to be defined. (rupress.org)
  • In this article we present evidence supporting the interaction between excitotoxicity, beta APP mismetabolism, metabolic compromise and intracellular calcium destabilization in the process of neurodegeneration associated with Alzheimer's disease (AD). (elsevier.com)
  • Expression of amyloid beta-protein precursor mRNAs in familial Alzheimer's disease. (ox.ac.uk)
  • It is an adapter protein that interacts with the Alzheimer's disease amyloid precursor protein. (nih.gov)
  • It interacts with the Alzheimer's disease amyloid precursor protein (APP), transcription factor CP2/LSF/LBP1 and the low-density lipoprotein receptor-related protein. (genecards.org)
  • This encoded protein could play an important role in the pathogenesis of Alzheimer's disease. (genecards.org)
  • [email protected]#To observe the effect of naoling decoction (NLD) on the behavior and the mRNA expression of beta- amyloid precursor protein (APP) in the hippocampus in rat model with Alzheimer's disease (AD). (bvsalud.org)
  • Disease severity can also be assessed by increased levels of CSF phospho-tau protein and the ratio of phospho-tau to Aβ (1-42), which might be a useful tool for predicting conversion of NPH individuals to other neurodegenerative disorders including Alzheimer's disease (AD). (elsevier.com)
  • A characteristic feature of Alzheimer's disease is the presence of large numbers of insoluble deposits, known as amyloid plaques, in the brains of those affected. (justia.com)
  • This beta-amyloid precursor protein (APP) knock-out strain offers a model useful in studies related to Alzheimer's disease. (jax.org)
  • The other main neuropathologic hallmarks of Alzheimer's disease are the neurofibrillary tangles of tau protein. (google.com)
  • Alzheimer's disease is not normally a hereditary disease, although cases linked to genetics share a common problem: a mutation in the genes that code for the presinilin proteins. (google.com)
  • Signaling Pathways: Amyloid Plaque and Neurofibrillary Tangle Formation in Alzheimer's Disease. (google.com)
  • The amyloid precursor protein (APP) plays a central role in Alzheimer's disease, but its actions in normal development are not well understood. (biologists.org)
  • Amyloid precursor protein (APP) is a transmembrane protein that plays a key role in Alzheimer's disease. (biologists.org)
  • A method useful in the diagnosis of Alzheimer's 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. (google.com.au)
  • More particularly, the present invention is a diagnostic assay based on the detection of proteolysis of the precursor to the Alzheimer's Disease beta-amyloid protein in the presence of a sample of cerebrospinal fluid or blood obtained from a patient to be tested. (google.com.au)
  • UCLA researchers have developed an immunotherapy that targets an alternate mechanism of amyloid beta (Aβ) toxicity for the treatment of Alzheimer's disease (AD). (universityofcalifornia.edu)
  • Senescence-accelerated mice (SAMP8) serve as a model for Alzheimer's disease (AD) as they exhibit early loss of memory and increased amyloid precursor protein (APP) expression. (biologists.org)
  • The antibody and antigen binding fragments thereof and methods disclosed are useful for diagnosis, prognosis and treatment of Alzheimer's disease or other .beta. (patents.com)
  • GSK3β Interactions with Amyloid Genes: An Autopsy Verification and Extension. (nih.gov)
  • The transcription factor specificity protein 1 (Sp1) is vital for the regulation of several genes involved in AD including APP and the beta site APP cleaving enzyme 1 (BACE1). (houstonmethodist.org)
  • This substitution is adjacent to the beta secretase cleavage site and results in a 40% reduction in the formation of amyloid beta in vitro. (wikipedia.org)
  • When APP molecules occupy a lipid raft region of membrane, they are more accessible to and differentially cleaved by beta secretase, whereas APP molecules outside a raft are differentially cleaved by the non-amyloidogenic alpha secretase. (wikipedia.org)
  • If alpha-secretase (α-secretase) acts on APP first instead of BACE, no amyloid beta is formed because α-secretase recognizes a target protein sequence closer to the cell surface than BACE. (wikipedia.org)
  • γ-secretase is actually a protein complex containing presenilin, nicastrin, APH-1, and PEN-2. (wikipedia.org)
  • To identify the cellular site of betaAPP phosphorylation, we took advantage of an antibody that specifically detects the free C terminus of beta-secretase-cleaved betaAPP containing the Swedish missense mutation (APPssw-beta). (uniprot.org)
  • Three secretase subtypes referred to as alpha, beta, and gamma have been identified based upon the region of amyloid protein precursor they cleave. (curehunter.com)
  • Α-secretase pathway: (1), also known as non-amyloid formation routes. (biology-online.org)
  • Followed by the alpha, gamma secretase cutting, resulting in the exocytosis of APP (s APP alpha), P3 ~ 40 (A beta 17 or A beta 17 ~ 42) fragment and APP intracellular domain fragment. (biology-online.org)
  • The role of the α-secretase enzyme sites in the region of A beta structure, it does not produce a complete A-beta fragment. (biology-online.org)
  • 2) β-secretase pathway: also known as amyloid formation routes. (biology-online.org)
  • Adapter protein that forms a transcriptionally active complex with the gamma-secretase-derived amyloid precursor protein (APP) intracellular domain. (uniprot.org)
  • We examined the cerebrospinal fluid (CSF) for alpha- and beta-secretase cleaved sAPP (alpha-sAPP and beta-sAPP) in 81 sporadic AD patients, 19 patients with mild cognitive impairment, and 42 healthy controls by using newly developed sandwich enzyme-linked immunosorbent assay methods. (lu.se)
  • Beta Secretase 1 (Aspartyl Protease 2 or Beta Site Amyloid Precursor Protein Cleaving Enzyme 1 or Memapsin 2 or Membrane Associated Aspartic Protease 2 or BACE1 or EC 3.4.23.46) pipeline Target constitutes close to 18 molecules. (researchandmarkets.com)
  • The latest report Beta Secretase 1 - Pipeline Review, H2 2018, outlays comprehensive information on the Beta Secretase 1 (Aspartyl Protease 2 or Beta Site Amyloid Precursor Protein Cleaving Enzyme 1 or Memapsin 2 or Membrane Associated Aspartic Protease 2 or BACE1 or EC 3.4.23.46) targeted therapeutics, complete with analysis by indications, stage of development, mechanism of action (MoA), route of administration (RoA) and molecule type. (researchandmarkets.com)
  • It also reviews key players involved in Beta Secretase 1 (Aspartyl Protease 2 or Beta Site Amyloid Precursor Protein Cleaving Enzyme 1 or Memapsin 2 or Membrane Associated Aspartic Protease 2 or BACE1 or EC 3.4.23.46) targeted therapeutics development with respective active and dormant or discontinued projects. (researchandmarkets.com)
  • Addressing both, we applied intravitreally a beta secretase (BACE) inhibitor in an AD mouse model (SwAPP/Psen1d9), and investigated possible clearance pathways for Aβ. (arvojournals.org)
  • Aβ is generated by sequential cleavage of the amyloid-β precursor protein (APP) by β- and then γ-secretase. (diva-portal.org)
  • Generation of βA4 by proteolytic processing of the amyloid precursor protein (APP) is thought to occur in a pathway that includes the activity of two as yet unknown proteases, with β-secretase cleaving at the N terminus and γ-secretase releasing the C terminus of βA4. (jneurosci.org)
  • Moreover, retention of APP695 proteins in the endoplasmic reticulum led to neither βA4 secretion nor to processing by β-secretase in human SH-SY5Y neuroblastoma cells. (jneurosci.org)
  • Primary cultures of rat brain cortical neurons were treated with OA and beta-secretase inhibitor. (bvsalud.org)
  • The suppression effect was alleviated markedly by pretreatment with beta-secretase inhibitor. (bvsalud.org)
  • AbetaPP level was increased further in neurons pretreated with beta-secretase inhibitor. (bvsalud.org)
  • In OA-induced tau phosphorylation cell model, inhibition of beta-secretase may protect neurons from death induced by OA. (bvsalud.org)
  • As apotential effective therapeutic target, beta-secretase is worth investigating further. (bvsalud.org)
  • APP is cleaved either by beta-secretase or by alpha-secretase to initiate amyloidogenic (release of A beta) or nonamyloidogenic processing of APP, respectively. (uni-muenchen.de)
  • Although APP inside raft clusters seems to be cleaved by beta-secretase, APP outside rafts undergoes cleavage by alpha-secretase. (uni-muenchen.de)
  • Thus, access of alpha- and beta-secretase to APP, and therefore A beta generation, may be determined by dynamic interactions of APP with lipid rafts. (uni-muenchen.de)
  • It is unclear how the generation of Aβ is regulated, but potentially there are several steps along the pathway in which other proteins could intervene, such as with the activity of the secretase enzymes or the metabolic fate of Aβ and its immediate precursor the APP βCTF. (jneurosci.org)
  • 8 Presenilins are a set of proteins that are part of the gamma secretase complex, which helps cleave APP to form Aβ. (google.com)
  • Beta secretase 1-dependent amyloid precursor protein processing promotes excessive vascular sprouting through NOTCH3 signalling. (babraham.ac.uk)
  • As PS1 has been shown to play a critical role in facilitating γ-secretase activity, and mutations in this protein are associated with familial AD (FAD), we have cloned it from SAMP8 mouse hippocampus and compared its sequence with those of other species. (biologists.org)
  • Inhibition studies and the finding that cell surface APP can serve as a direct precursor of βA4 suggest that the endosomal/lysosomal compartment is involved in the proteolysis of APP into βA4. (jneurosci.org)
  • The beta-amyloid precursor protein (betaAPP) is a transmembrane protein that is exclusively phosphorylated on serine residues within its ectodomain. (uniprot.org)
  • Formalin-fixed, paraffin-embedded 5µm sections of 30 optic nerves and retinas from 15 donors previously diagnosed with AD and 30 age-matched control optic nerves and retinas from 15 individuals with no AD, other neurodegenerative diseases, diabetes mellitus, or sepsis were stained with antibodies reactive against amyloid-beta (AB) and amyloid precursor protein (APP). (arvojournals.org)
  • By visualizing the distribution of beta PP monoclonal antibodies added to intact cultures, beta PP was shown to be internalized from distal axons or terminals and retrogradely transported back to perikarya in organelles which colocalized with fluid-phase endocytic markers. (rupress.org)
  • APP and the beta-site APP cleavage enzyme (BACE1) could be induced to copatch at the plasma membrane upon cross-linking with antibodies and to segregate away from nonraft markers. (uni-muenchen.de)
  • Brain and retina sections and retinal whole-mounts of non-injected animals were also immunostained for Aβ 40/42 in combination with podoplanin (lymphatic vessel marker), or low density lipoprotein receptor-related protein 1 (LRP-1, involved in Aβ clearance in the brain), and IDE (insulin degrading enzyme, involved in Aβ cleavage) in brain sections. (arvojournals.org)
  • Description: This is Double-antibody Sandwich Enzyme-linked immunosorbent assay for detection of Human Amyloid Beta Precursor Like Protein 2 (APLP2) in tissue homogenates, cell lysates and other biological fluids. (glideruniversity.org)
  • Description: Enzyme-linked immunosorbent assay based on the Double-antibody Sandwich method for detection of Human Amyloid Beta Precursor Like Protein 2 (APLP2) in samples from tissue homogenates, cell lysates and other biological fluids with no significant corss-reactivity with analogues from other species. (glideruniversity.org)
  • We exposed APP-PS1-HEK293 cells to ICT to investigate its effect on beta-site amyloid cleaving enzyme (BACE)1. (peerj.com)
  • The BACE1 enzyme is key in the development of amyloid beta, prices of protein that clump together and over time lead to a buildup of amyloid plaque in the brain. (yahoo.com)
  • Successful demonstration that select Aβ variants and chiral substitutions have differing selectivity for ADAM10, the enzyme of interest that generates soluble amyloid precursor protein alpha (sAPPα). (universityofcalifornia.edu)
  • These mice support a primary role for APP/A beta in the genesis of AD and could provide a preclinical model for testing therapeutic drugs. (nih.gov)
  • Tg2576 mice (Tg(APPSWE)2576Kha), which express human [beta]-amyloid precursor proteins (hAPP) containing the K670N and M671L mutations on a 129S6 genetic background, were purchased from Taconic Farms, Inc. (Hudson, NY, USA) [11]. (thefreelibrary.com)
  • PS2M1 mice express human PS2 proteins containing the N141I mutation on a C57BL/6JJcl background (purchased from Immuno-Biological Laboratories Co, Ltd., Fujioka, Japan) [22, 23]. (thefreelibrary.com)
  • We show that after a chronic 8 week treatment, benfotiamine dose-dependently enhanced the spatial memory of amyloid precursor protein/presenilin-1 mice in the Morris water maze test. (unboundmedicine.com)
  • Furthermore, benfotiamine effectively reduced both amyloid plaque numbers and phosphorylated tau levels in cortical areas of the transgenic mice brains. (unboundmedicine.com)
  • After 8 days retina samples of adult SwAPP/Psen1d9 and wild-type C57BL/6 mice (healthy wt controls) were embedded in paraffin or were lysed for protein analyses. (arvojournals.org)
  • These studies showed that all three BACE1 inhibitors decreased brain Abeta1-40 in P-gp KO mice, demonstrating that P-gp is a major limitation for development of BACE1 inhibitors to test the amyloid hypothesis. (geoscience.net)
  • We have previously reported that tolfenamic acid promotes the degradation of Sp1 protein (SP1) in pancreatic human cancer cells and mice tumors. (houstonmethodist.org)
  • 1995. beta-Amyloid precursor protein-deficient mice show reactive gliosis and decreased locomotor activity. (jax.org)
  • Also, this antibody has been used to neutralize Aβ assemblies in brains of transgenic mice expressing a mutant form of amyloid precursor protein, and for in vivo deep tissue imaging using near-IR optical spectrum. (sigmaaldrich.com)
  • Significantly fewer vascular amyloid deposits and microhemorrhages were observed in mice administered the de-2H6 antibody compared with those receiving unmodified 2H6 antibody. (unboundmedicine.com)
  • Partial inhibition of complex I triggers the AMP-activated protein kinase-dependent signaling network leading to neuroprotection in symptomatic APP/PS1 female mice, a translational model of AD. (nature.com)
  • Antibody cross-linking dramatically increased production of A beta in a cholesterol-dependent manner. (uni-muenchen.de)
  • The antibody reacts specifically with β-amyloid protein. (sigmaaldrich.com)
  • The epitope recognized by the antibody resides within amino acids 1-12 of the β-amyloid protein. (sigmaaldrich.com)
  • Monoclonal Anti-β-Amyloid antibody has been used in immunoprecipitation analysis, microarray-based immunoassay and microarray. (sigmaaldrich.com)
  • Human amyloid related protein monoclonal antibody. (freepatentsonline.com)
  • The invention provides an antibody or antigen binding fragments thereof that binds to 3pE A.beta. (patents.com)
  • 1. An isolated antibody or antigen binding fragment thereof which binds to 3pE A.beta. (patents.com)
  • Immunohistochemical staining for beta-amyloid precursor protein (betaAPP) is a well-established marker of traumatic axonal injury in adults. (nih.gov)
  • Also, mRNA expression of A disintegrin and metalloproteinase domain-containing protein 10 (ADAM10) increased, while that of BACE1 and presenilin-1 (PS1) decreased, upon ICT treatment. (peerj.com)
  • Western blotting and immunofluorescence confirmed that protein expression of ADAM10, BACE1 and PS1 showed the same trend. (peerj.com)
  • Recent studies implicate human amylin aggregates cause proteotoxicity (cell death induced by misfolded proteins) in both the brain and the heart. (springer.com)
  • are associated with the deposition of protein aggregates in the diseased tissues. (bakerlab.org)
  • Among its related pathways are DNA Double Strand Break Response and Respiratory electron transport, ATP synthesis by chemiosmotic coupling, and heat production by uncoupling proteins. . (genecards.org)
  • The major molecules involved in these pathways include: glial cells (specifically astrocytes and microglia), beta-amyloid, and pro-inflammatory compounds. (wikipedia.org)
  • It is a key structural component of a great number of proteins, and a co-factor of more than 300 enzymes that regulate a variety of cellular processes and cellular signaling pathways essential for both brain and systemic physiology ( Takeda, 2000 ). (frontiersin.org)
  • May interact with cellular G-protein signaling pathways. (abcam.com)
  • AD brains contain numerous amyloid plaques surrounded by dystrophic neurites, and show profound synaptic loss, neurofibrillary tangle formation and gliosis. (nih.gov)
  • Increased APP phosphorylation and altered expression levels of the brain enriched Fe65 protein have been observed in the brains of AD patients. (diva-portal.org)
  • The 50 % reduction in phenylalanine and tyrosine in HIP brains is significant given their role in supporting brain chemistry as a precursor for catecholamines (dopamine, norepinephrine, epinephrine), which may contribute to the increased morbidity and mortality in diabetics at a multi-system level beyond the effects on glucose metabolism. (springer.com)
  • Autopsies have shown that amyloid plaques are found in the brains of virtually all Alzheimer's patients and that the degree of amyloid plaque deposition correlates with the degree of dementia (Cummings & Cotman, 1995, Lancet 326:1524-1587). (justia.com)
  • We perform a single molecule level study of the RERMS sequence of amyloid $\beta $/A4 precursor protein fragment on a clean Ag(111) surface using a low-temperature scanning-tunneling-microscope (STM) system at 5K. (aps.org)
  • Moreover, we are able to form a well ordered two-dimensional layer of the protein fragment by increasing the deposition time. (aps.org)
  • After OA treatment , both AbetaPP and beta-C-terminal fragment (betaCTF) were significantly increased in neurons . (bvsalud.org)
  • The first prediction jobs will focus on the Alzheimer\'s beta(1-40) fragment. (bakerlab.org)
  • We are working on building high-resolution predictions for medically relevant amyloids, starting with the Alzheimer\'s-beta fragment (1-40). (bakerlab.org)
  • These data indicate that protein phosphorylation regulates intra-beta/A4 amyloid cleavage and APP secretion. (pnas.org)
  • Ectodomain phosphorylation of beta-amyloid precursor protein at two distinct cellular locations. (uniprot.org)
  • Most notably, benfotiamine, but not fursultiamine, significantly elevated the phosphorylation level of glycogen synthase kinase-3alpha and -3beta, and reduced their enzymatic activities in the amyloid precursor protein/presenilin-1 transgenic brain. (unboundmedicine.com)
  • The processing of amyloid -beta precursor protein (AbetaPP) in okadaic acid (OA)-induced tau phosphorylation primary neurons was studied. (bvsalud.org)
  • May play a role in intracellular protein transport. (genecards.org)
  • This cellular zinc homeostasis results from the actions of a coordinated regulation effected by different proteins involved in the uptake, excretion and intracellular storage/trafficking of zinc. (frontiersin.org)
  • These proteins include membranous transporters (ZnT and Zip) and metallothioneins (MT) which control intracellular zinc levels. (frontiersin.org)
  • Cellular Actions of Beta-amyloid Precursor Protein and Its Soluble and Fibrillogenic Derivatives. (google.com)
  • X11L2, a new member of the X11 protein family, interacts with Alzheimer's beta-amyloid precursor protein. (wikigenes.org)
  • Deposits of amyloid can be seen in sections of brain tissue. (wikipedia.org)
  • The dissociated tau protein becomes tangled and deposits inside the cell. (google.com)
  • The expectation is that knowledge of the high-resolution structure of amyloid fibrils will aid in the design of small molecules which can inhibit fibril formation and/or break down existing deposits. (bakerlab.org)
  • It specifically stains amyloid plaques within the cortex and amyloid deposits in blood vessels using formic acid-treated, formalin-fixed, paraffin-embedded, and Methacarn-fixed sections of human Alzheimer′s disease (AD) brain tissue. (sigmaaldrich.com)
  • Among other roles in the cell, secretases act on the amyloid-beta precursor protein (APP) to cleave the protein into three fragments. (wikipedia.org)
  • The mechanical stability of individual protein fragments are checked by laterally manipulating them with the STM tip. (aps.org)
  • Measuring the levels of a series of C-terminal APP fragments generated by enzymatic cutting at different APP-cleavage sites showed that both beta- and alpha-cleavage of APP were inhibited by zinc influx. (yonsei.ac.kr)
  • Reduced Aβ production was not attributable to altered β-amyloid precursor protein (APP) ectodomain shedding but was a result of an enhanced degradation of APP C-terminal fragments (CTFs) in the absence of PAFAH1B2 but not its close homolog PAFAH1B3. (jneurosci.org)
  • One of the fragments produced in this cutting process is β-amyloid. (wikipedia.org)
  • Secreted forms of APP found in blood plasma and cerebrospinal fluid arise by proteolytic cleavage of APP within the beta/A4 amyloid domain, precluding the possibility of amyloidogenesis for that population of molecules. (pnas.org)
  • Rab6 interacts with the mint3 adaptor protein. (wikigenes.org)
  • APPBP2 interacts with microtubules and is functionally associated with beta-amyloid precursor. (biomol.com)
  • Amyloid-beta precursor protein (APP) is an integral membrane protein expressed in many tissues and concentrated in the synapses of neurons. (wikipedia.org)
  • Trafficking of cell surface beta-amyloid precursor protein: retrograde and transcytotic transport in cultured neurons. (rupress.org)
  • In this study, we describe a detailed localization of cell surface beta PP and its subsequent trafficking in primary cultured neurons. (rupress.org)
  • Retrograde transport of beta PP was shown in both hippocampal and peripheral sympathetic neurons, the latter using a compartment culture system that isolated cell bodies from distal axons and terminals. (rupress.org)
  • In addition, we demonstrated that beta PP from distal axons was transcytotically transported to the surface of perikarya from distal axons in sympathetic neurons. (rupress.org)
  • Indirect evidence of this transcytotic pathway was obtained in hippocampal neurons using antisense oligonucleotide to the kinesin heavy chain to inhibit anterograde beta PP transport. (rupress.org)
  • Taken together, these results demonstrate novel aspects of beta PP trafficking in neurons, including retrograde axonal transport and transcytosis. (rupress.org)
  • 3 Eventually, the degenerate neurons become clumped into the amyloid plaques which are insoluble and unable to be broken down by the body. (google.com)
  • Normally, tau proteins serve to stabilize microtubules in the neurons in the brain, and are essential for axonal growth and development. (google.com)
  • Beta-amyloid and Its Damaging Effects on Neurons. (google.com)
  • Besides their involvement in the pathogenesis of Alzheimer's, these proteins also have other functional roles in the cell. (wikipedia.org)
  • One approach toward treatment has been to develop immunotherapies that target and remove the buildup of amyloid beta (Aβ) plaques in the brain that are associated with AD. (universityofcalifornia.edu)
  • Thus, we have identified an important protein that can selectively modify Aβ generation via a novel mechanism, namely enhanced degradation of its immediate precursor. (jneurosci.org)
  • We are trying to build high-resolution models of the fibrils formed by medically-relevant amyloids. (bakerlab.org)
  • Amyloid beta a4 precursor protein-binding family B member 1 (FE65) interactomics revealed synaptic vesicle glycoprotein 2A (SV2A) and sarcoplasmic/endoplasmic reticulum calcium ATPase 2 (SERCA2) as new binding proteins in the human brain. (harvard.edu)
  • Aβ was located around and in blood vessels, suggesting a cerebral amyloid angiopathy in this model. (arvojournals.org)
  • Effects of ICT on the mRNA expression of APP were assessed by quantitative polymerase chain reaction, and protein expression was measured by western blotting and immunofluorescence. (peerj.com)
  • [email protected]#NLD can lower the expression of APP mRNA to reduce beta-amyloid protein deposition of rat hippocampus , which may be one of the mechanisms of improving the learning and memory capacity of AD model rats . (bvsalud.org)
  • Mus musculus amyloid beta (A4) precursor protein (App), transcript variant 1, mRNA. (jax.org)
  • The presence of β-amyloid plaques in the brain causes the body to recruit and activate microglial cells and astrocytes. (wikipedia.org)
  • 3. The method of claim 1 wherein said amyloid precursor protein (APP) substrate comprises a recombinantly expressed polypeptide. (google.com.au)
  • We found that neither the level of CSF-alpha-sAPP nor CSF-beta-sAPP differed between sporadic AD patients and healthy controls. (lu.se)
  • However, the level of CSF-beta-sAPP was significantly increased in patients with mild cognitive impairment compared to controls. (lu.se)
  • We investigate how ICT affects secretion of amyloid precursor protein (APP). (peerj.com)
  • A primary pathogenic role for APP/A beta is suggested by missense mutations in APP that are tightly linked to autosomal dominant forms of AD. (nih.gov)
  • These mutations are located within or immediately flanking the A beta region of beta-APP, but the mechanism by which they cause the pathological phenotype of early and accelerated A beta deposition is unknown. (nih.gov)
  • In vitro binding studies revealed direct interactions among multiple members of the APP and contactin protein families. (biologists.org)
  • Functional assays revealed regulatory effects of both APP and contactin 4 on NgCAM-dependent growth of cultured retinal axons, demonstrating specific functional interactions among these proteins. (biologists.org)
  • These studies identify novel binding and functional interactions among proteins of the APP, contactin and L1CAM families, with general implications for mechanisms of APP action in neural development and disease. (biologists.org)
  • Interactions of pathological hallmark proteins: Tubulin polymerization promoting protein/p25, β-amyloid and α-synuclein. (sigmaaldrich.com)
  • Note that the 'protein existence' evidence does not give information on the accuracy or correctness of the sequence(s) displayed. (uniprot.org)
  • Protein family classification is often achieved using computerised multiple protein sequence alignment and structural analysis. (ebi.ac.uk)