Amyloid beta-Protein Precursor: A single-pass type I membrane protein. It is cleaved by AMYLOID PRECURSOR PROTEIN SECRETASES to produce peptides of varying amino acid lengths. A 39-42 amino acid peptide, AMYLOID BETA-PEPTIDES is a principal component of the extracellular amyloid in SENILE PLAQUES.Amyloid beta-Peptides: Peptides generated from AMYLOID BETA-PEPTIDES PRECURSOR. An amyloid fibrillar form of these peptides is the major component of amyloid plaques found in individuals with Alzheimer's disease and in aged individuals with trisomy 21 (DOWN SYNDROME). The peptide is found predominantly in the nervous system, but there have been reports of its presence in non-neural tissue.Amyloid: A fibrous protein complex that consists of proteins folded into a specific cross beta-pleated sheet structure. This fibrillar structure has been found as an alternative folding pattern for a variety of functional proteins. Deposits of amyloid in the form of AMYLOID PLAQUES are associated with a variety of degenerative diseases. The amyloid structure has also been found in a number of functional proteins that are unrelated to disease.Alzheimer Disease: A degenerative disease of the BRAIN characterized by the insidious onset of DEMENTIA. Impairment of MEMORY, judgment, attention span, and problem solving skills are followed by severe APRAXIAS and a global loss of cognitive abilities. The condition primarily occurs after age 60, and is marked pathologically by severe cortical atrophy and the triad of SENILE PLAQUES; NEUROFIBRILLARY TANGLES; and NEUROPIL THREADS. (From Adams et al., Principles of Neurology, 6th ed, pp1049-57)Protein PrecursorsPeptide Fragments: Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.Amyloid Precursor Protein Secretases: Endopeptidases that are specific for AMYLOID PROTEIN PRECURSOR. Three secretase subtypes referred to as alpha, beta, and gamma have been identified based upon the region of amyloid protein precursor they cleave.Smilacaceae: A plant family of the order Liliales, subclass Liliidae, class Liliopsida (monocotyledon).Plaque, Amyloid: Accumulations of extracellularly deposited AMYLOID FIBRILS within tissues.Cerebral Amyloid Angiopathy: A heterogeneous group of sporadic or familial disorders characterized by AMYLOID deposits in the walls of small and medium sized blood vessels of CEREBRAL CORTEX and MENINGES. Clinical features include multiple, small lobar CEREBRAL HEMORRHAGE; cerebral ischemia (BRAIN ISCHEMIA); and CEREBRAL INFARCTION. Cerebral amyloid angiopathy is unrelated to generalized AMYLOIDOSIS. Amyloidogenic peptides in this condition are nearly always the same ones found in ALZHEIMER DISEASE. (from Kumar: Robbins and Cotran: Pathologic Basis of Disease, 7th ed., 2005)Aspartic Acid Endopeptidases: A sub-subclass of endopeptidases that depend on an ASPARTIC ACID residue for their activity.Amyloid Neuropathies: Disorders of the peripheral nervous system associated with the deposition of AMYLOID in nerve tissue. Familial, primary (nonfamilial), and secondary forms have been described. Some familial subtypes demonstrate an autosomal dominant pattern of inheritance. Clinical manifestations include sensory loss, mild weakness, autonomic dysfunction, and CARPAL TUNNEL SYNDROME. (Adams et al., Principles of Neurology, 6th ed, p1349)Moraceae: The mulberry plant family of the order Urticales, subclass Hamamelidae, class Magnoliopsida. They have milky latex and small, petalless male or female flowers.Endopeptidases: A subclass of PEPTIDE HYDROLASES that catalyze the internal cleavage of PEPTIDES or PROTEINS.Brain: The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM.Iridoid Glycosides: A subclass of iridoid compounds that include a glycoside moiety, usually found at the C-1 position.Molecular Sequence Data: Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.Serum Amyloid A Protein: An ACUTE PHASE REACTION protein present in low concentrations in normal sera, but found at higher concentrations in sera of older persons and in patients with AMYLOIDOSIS. It is the circulating precusor of amyloid A protein, which is found deposited in AA type AMYLOID FIBRILS.Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM.Mice, Transgenic: Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Cells, Cultured: Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.Cerebral Cortex: The thin layer of GRAY MATTER on the surface of the CEREBRAL HEMISPHERES that develops from the TELENCEPHALON and folds into gyri and sulchi. It reaches its highest development in humans and is responsible for intellectual faculties and higher mental functions.Protein Processing, Post-Translational: Any of various enzymatically catalyzed post-translational modifications of PEPTIDES or PROTEINS in the cell of origin. These modifications include carboxylation; HYDROXYLATION; ACETYLATION; PHOSPHORYLATION; METHYLATION; GLYCOSYLATION; ubiquitination; oxidation; proteolysis; and crosslinking and result in changes in molecular weight and electrophoretic motility.Amyloidosis: A group of sporadic, familial and/or inherited, degenerative, and infectious disease processes, linked by the common theme of abnormal protein folding and deposition of AMYLOID. As the amyloid deposits enlarge they displace normal tissue structures, causing disruption of function. Various signs and symptoms depend on the location and size of the deposits.Disease Models, Animal: Naturally occurring or experimentally induced animal diseases with pathological processes sufficiently similar to those of human diseases. They are used as study models for human diseases.Islet Amyloid Polypeptide: A pancreatic beta-cell hormone that is co-secreted with INSULIN. It displays an anorectic effect on nutrient metabolism by inhibiting gastric acid secretion, gastric emptying and postprandial GLUCAGON secretion. Islet amyloid polypeptide can fold into AMYLOID FIBRILS that have been found as a major constituent of pancreatic AMYLOID DEPOSITS.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.Aging: The gradual irreversible changes in structure and function of an organism that occur as a result of the passage of time.Interleukin-1beta: An interleukin-1 subtype that is synthesized as an inactive membrane-bound pro-protein. Proteolytic processing of the precursor form by CASPASE 1 results in release of the active form of interleukin-1beta from the membrane.RNA, Messenger: RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.Presenilin-1: Integral membrane protein of Golgi and endoplasmic reticulum. Its homodimer is an essential component of the gamma-secretase complex that catalyzes the cleavage of membrane proteins such as NOTCH RECEPTORS and AMYLOID BETA-PEPTIDES precursors. PSEN1 mutations cause early-onset ALZHEIMER DISEASE type 3 that may occur as early as 30 years of age in humans.Serum Amyloid P-Component: Amyloid P component is a small, non-fibrillar glycoprotein found in normal serum and in all amyloid deposits. It has a pentagonal (pentaxin) structure. It is an acute phase protein, modulates immunologic responses, inhibits ELASTASE, and has been suggested as an indicator of LIVER DISEASE.Mutation: Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.Congo Red: An acid dye used in testing for hydrochloric acid in gastric contents. It is also used histologically to test for AMYLOIDOSIS.Insulysin: An enzyme the catalyzes the degradation of insulin, glucagon and other polypeptides. It is inhibited by bacitracin, chelating agents EDTA and 1,10-phenanthroline, and by thiol-blocking reagents such as N-ethylmaleimide, but not phosphoramidon. (Eur J Biochem 1994;223:1-5) EC 3.4.24.56.Recombinant Proteins: Proteins prepared by recombinant DNA technology.Cloning, Molecular: The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells.Vitellogenins: Phospholipoglycoproteins produced in the fat body of egg-laying animals such as non-mammalian VERTEBRATES; ARTHROPODS; and others. Vitellogenins are secreted into the HEMOLYMPH, and taken into the OOCYTES by receptor-mediated ENDOCYTOSIS to form the major yolk proteins, VITELLINS. Vitellogenin production is under the regulation of steroid hormones, such as ESTRADIOL and JUVENILE HORMONES in insects.Kinetics: The rate dynamics in chemical or physical systems.S100 Calcium Binding Protein beta Subunit: A calcium-binding protein that is 92 AA long, contains 2 EF-hand domains, and is concentrated mainly in GLIAL CELLS. Elevation of S100B levels in brain tissue correlates with a role in neurological disorders.Vitellogenesis: The active production and accumulation of VITELLINS (egg yolk proteins) in the non-mammalian OOCYTES from circulating precursors, VITELLOGENINS. Vitellogenesis usually begins after the first MEIOSIS and is regulated by estrogenic hormones.Peptides: Members of the class of compounds composed of AMINO ACIDS joined together by peptide bonds between adjacent amino acids into linear, branched or cyclical structures. OLIGOPEPTIDES are composed of approximately 2-12 amino acids. Polypeptides are composed of approximately 13 or more amino acids. PROTEINS are linear polypeptides that are normally synthesized on RIBOSOMES.beta 2-Microglobulin: An 11-kDa protein associated with the outer membrane of many cells including lymphocytes. It is the small subunit of the MHC class I molecule. Association with beta 2-microglobulin is generally required for the transport of class I heavy chains from the endoplasmic reticulum to the cell surface. Beta 2-microglobulin is present in small amounts in serum, csf, and urine of normal people, and to a much greater degree in the urine and plasma of patients with tubular proteinemia, renal failure, or kidney transplants.Transfection: The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.Presenilin-2: Integral membrane protein of Golgi and endoplasmic reticulum. Its homodimer is an essential component of the gamma-secretase complex that catalyzes the cleavage of membrane proteins such as NOTCH RECEPTORS and AMYLOID BETA-PEPTIDES precursors. PSEN2 mutations cause ALZHEIMER DISEASE type 4.ThiazolesBlotting, Western: Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.tau Proteins: Microtubule-associated proteins that are mainly expressed in neurons. Tau proteins constitute several isoforms and play an important role in the assembly of tubulin monomers into microtubules and in maintaining the cytoskeleton and axonal transport. Aggregation of specific sets of tau proteins in filamentous inclusions is the common feature of intraneuronal and glial fibrillar lesions (NEUROFIBRILLARY TANGLES; NEUROPIL THREADS) in numerous neurodegenerative disorders (ALZHEIMER DISEASE; TAUOPATHIES).Neurofibrillary Tangles: Abnormal structures located in various parts of the brain and composed of dense arrays of paired helical filaments (neurofilaments and microtubules). These double helical stacks of transverse subunits are twisted into left-handed ribbon-like filaments that likely incorporate the following proteins: (1) the intermediate filaments: medium- and high-molecular-weight neurofilaments; (2) the microtubule-associated proteins map-2 and tau; (3) actin; and (4) UBIQUITINS. As one of the hallmarks of ALZHEIMER DISEASE, the neurofibrillary tangles eventually occupy the whole of the cytoplasm in certain classes of cell in the neocortex, hippocampus, brain stem, and diencephalon. The number of these tangles, as seen in post mortem histology, correlates with the degree of dementia during life. Some studies suggest that tangle antigens leak into the systemic circulation both in the course of normal aging and in cases of Alzheimer disease.Membrane Proteins: Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.
The amyloid precursor protein interacts with Go heterotrimeric protein within a cell compartment specialized in signal transduction. (1/2953)
The function of the beta-amyloid protein precursor (betaAPP), a transmembrane molecule involved in Alzheimer pathologies, is poorly understood. We recently reported the presence of a fraction of betaAPP in cholesterol and sphingoglycolipid-enriched microdomains (CSEM), a caveolae-like compartment specialized in signal transduction. To investigate whether betaAPP actually interferes with cell signaling, we reexamined the interaction between betaAPP and Go GTPase. In strong contrast with results obtained with reconstituted phospholipid vesicles (Okamoto et al., 1995), we find that incubating total neuronal membranes with 22C11, an antibody that recognizes an N-terminal betaAPP epitope, reduces high-affinity Go GTPase activity. This inhibition is specific of Galphao and is reproduced, in the absence of 22C11, by the addition of the betaAPP C-terminal domain but not by two distinct mutated betaAPP C-terminal domains that do not bind Galphao. This inhibition of Galphao GTPase activity by either 22C11 or wild-type betaAPP cytoplasmic domain suggests that intracellular interactions between betaAPP and Galphao could be regulated by extracellular signals. To verify whether this interaction is preserved in CSEM, we first used biochemical, immunocytochemical, and ultrastructural techniques to unambiguously confirm the colocalization of Galphao and betaAPP in CSEM. We show that inhibition of basal Galphao GTPase activity also occurs within CSEM and correlates with the coimmunoprecipitation of Galphao and betaAPP. The regulation of Galphao GTPase activity by betaAPP in a compartment specialized in signaling may have important consequences for our understanding of the physiopathological functions of betaAPP. (+info)Proteolytic processing of the Alzheimer's disease amyloid precursor protein within its cytoplasmic domain by caspase-like proteases. (2/2953)
Alzheimer's disease is characterized by neurodegeneration and deposition of betaA4, a peptide that is proteolytically released from the amyloid precursor protein (APP). Missense mutations in the genes coding for APP and for the polytopic membrane proteins presenilin (PS) 1 and PS2 have been linked to familial forms of early-onset Alzheimer's disease. Overexpression of presenilins, especially that of PS2, induces increased susceptibility for apoptosis that is even more pronounced in cells expressing presenilin mutants. Additionally, presenilins themselves are targets for activated caspases in apoptotic cells. When we analyzed APP in COS-7 cells overexpressing PS2, we observed proteolytic processing close to the APP carboxyl terminus. Proteolytic conversion was increased in the presence of PS2-I, which encodes one of the known PS2 pathogenic mutations. The same proteolytic processing occurred in cells treated with chemical inducers of apoptosis, suggesting a participation of activated caspases in the carboxyl-terminal truncation of APP. This was confirmed by showing that specific caspase inhibitors blocked the apoptotic conversion of APP. Sequence analysis of the APP cytosolic domain revealed a consensus motif for group III caspases ((IVL)ExD). Mutation of the corresponding Asp664 residue abolished cleavage, thereby identifying APP as a target molecule for caspase-like proteases in the pathways of programmed cellular death. (+info)Translation of the alzheimer amyloid precursor protein mRNA is up-regulated by interleukin-1 through 5'-untranslated region sequences. (3/2953)
The amyloid precursor protein (APP) has been associated with Alzheimer's disease (AD) because APP is processed into the beta-peptide that accumulates in amyloid plaques, and APP gene mutations can cause early onset AD. Inflammation is also associated with AD as exemplified by increased expression of interleukin-1 (IL-1) in microglia in affected areas of the AD brain. Here we demonstrate that IL-1alpha and IL-1beta increase APP synthesis by up to 6-fold in primary human astrocytes and by 15-fold in human astrocytoma cells without changing the steady-state levels of APP mRNA. A 90-nucleotide sequence in the APP gene 5'-untranslated region (5'-UTR) conferred translational regulation by IL-1alpha and IL-1beta to a chloramphenicol acetyltransferase (CAT) reporter gene. Steady-state levels of transfected APP(5'-UTR)/CAT mRNAs were unchanged, whereas both base-line and IL-1-dependent CAT protein synthesis were increased. This APP mRNA translational enhancer maps from +55 to +144 nucleotides from the 5'-cap site and is homologous to related translational control elements in the 5'-UTR of the light and and heavy ferritin genes. Enhanced translation of APP mRNA provides a mechanism by which IL-1 influences the pathogenesis of AD. (+info)Early phenotypic changes in transgenic mice that overexpress different mutants of amyloid precursor protein in brain. (4/2953)
Transgenic mice overexpressing different forms of amyloid precursor protein (APP), i.e. wild type or clinical mutants, displayed an essentially comparable early phenotype in terms of behavior, differential glutamatergic responses, deficits in maintenance of long term potentiation, and premature death. The cognitive impairment, demonstrated in F1 hybrids of the different APP transgenic lines, was significantly different from nontransgenic littermates as early as 3 months of age. Biochemical analysis of secreted and membrane-bound APP, C-terminal "stubs," and Abeta(40) and Abeta(42) peptides in brain indicated that no single intermediate can be responsible for the complex of phenotypic dysfunctions. As expected, the Abeta(42) levels were most prominent in APP/London transgenic mice and correlated directly with the formation of amyloid plaques in older mice of this line. Plaques were associated with immunoreactivity for hyperphosphorylated tau, eventually signaling some form of tau pathology. In conclusion, the different APP transgenic mouse lines studied display cognitive deficits and phenotypic traits early in life that dissociated in time from the formation of amyloid plaques and will be good models for both early and late neuropathological and clinical aspects of Alzheimer's disease. (+info)Amyloid precursor protein metabolism in fibroblasts from individuals with one, two or three copies of the amyloid precursor protein (APP) gene. (5/2953)
Protein kinase C (PKC)-activated modulation of amyloid precursor protein (APP) metabolism has been investigated in natural models of altered APP expression due to the presence of one, two or three copies of the APP gene. We show that levels of APP present in human skin fibroblasts strongly influence the effect of PKC activation of soluble APP (sAPP) release. Thus fibroblasts derived from a patient with a deletion in chromosome 21 including the APP locus (Delta21) had lower levels of both APP mRNA and cell-associated APP, and showed an exaggerated phorbol-ester-induced sAPP release, when compared with fibroblasts from control individuals. In contrast, fibroblasts from chromosome 21 trisomic Down's syndrome patients failed to show a concentration-dependent response to phorbol ester treatment. These results suggest that the levels of APP expression can affect the degree of response to PKC-mediated modulation of the metabolism of this protein. (+info)Regulation of beta-amyloid secretion by FE65, an amyloid protein precursor-binding protein. (6/2953)
The principal component of Alzheimer's amyloid plaques, Abeta, derives from proteolytic processing of the Alzheimer's amyloid protein precursor (APP). FE65 is a brain-enriched protein that binds to APP. Although several laboratories have characterized the APP-FE65 interaction in vitro, the possible relevance of this interaction to Alzheimer's disease has remained unclear. We demonstrate here that APP and FE65 co-localize in the endoplasmic reticulum/Golgi and possibly in endosomes. Moreover, FE65 increases translocation of APP to the cell surface, as well as both alphaAPPs and Abeta secretion. The dramatic (4-fold) FE65-dependent increase in Abeta secretion suggests that agents which inhibit the interaction of FE65 with APP might reduce Abeta secretion in the brain and therefore be useful for preventing or slowing amyloid plaque formation. (+info)Mechanism of the cleavage specificity of Alzheimer's disease gamma-secretase identified by phenylalanine-scanning mutagenesis of the transmembrane domain of the amyloid precursor protein. (7/2953)
Proteolytic processing of the amyloid precursor protein by beta-secretase yields A4CT (C99), which is cleaved further by the as yet unknown gamma-secretase, yielding the beta-amyloid (Abeta) peptide with 40 (Abeta40) or 42 residues (Abeta42). Because the position of gamma-secretase cleavage is crucial for the pathogenesis of Alzheimer's disease, we individually replaced all membrane-domain residues of A4CT outside the Abeta domain with phenylalanine, stably transfected the constructs in COS7 cells, and determined the effect of these mutations on the cleavage specificity of gamma-secretase (Abeta42/Abeta40 ratio). Compared with wild-type A4CT, mutations at Val-44, Ile-47, and Val-50 led to decreased Abeta42/Abeta40 ratios, whereas mutations at Thr-43, Ile-45, Val-46, Leu-49, and Met-51 led to increased Abeta42/Abeta40 ratios. A massive effect was observed for I45F (34-fold increase) making this construct important for the generation of animal models for Alzheimer's disease. Unlike the other mutations, A4CT-V44F was processed mainly to Abeta38, as determined by mass spectrometry. Our data provide a detailed model for the active site of gamma-secretase: gamma-secretase interacts with A4CT by binding to one side of the alpha-helical transmembrane domain of A4CT. Mutations in the transmembrane domain of A4CT interfere with the interaction between gamma-secretase and A4CT and, thus, alter the cleavage specificity of gamma-secretase. (+info)Plaque-independent disruption of neural circuits in Alzheimer's disease mouse models. (8/2953)
Autosomal dominant forms of familial Alzheimer's disease (FAD) are associated with increased production of the amyloid beta peptide, Abeta42, which is derived from the amyloid protein precursor (APP). In FAD, as well as in sporadic forms of the illness, Abeta peptides accumulate abnormally in the brain in the form of amyloid plaques. Here, we show that overexpression of FAD(717V-->F)-mutant human APP in neurons of transgenic mice decreases the density of presynaptic terminals and neurons well before these mice develop amyloid plaques. Electrophysiological recordings from the hippocampus revealed prominent deficits in synaptic transmission, which also preceded amyloid deposition by several months. Although in young mice, functional and structural neuronal deficits were of similar magnitude, functional deficits became predominant with advancing age. Increased Abeta production in the context of decreased overall APP expression, achieved by addition of the Swedish FAD mutation to the APP transgene in a second line of mice, further increased synaptic transmission deficits in young APP mice without plaques. These results suggest a neurotoxic effect of Abeta that is independent of plaque formation. (+info)... skeletal muscle-specific Ca2+/calmodulin-dependent protein kinase; Akt; Beta-amyloid precursor protein (betaAPP); Huntingtin. ... For example, GAPDH interactions with beta-amyloid precursor protein (betaAPP) could interfere with its function regarding the ... GAPDH participates in a number of biological functions through its protein-protein interactions with: tubulin to facilitate ... where it ubiquitinates and degrades nuclear proteins during nitrosative stress conditions; GAPDH's competitor of Siah protein ...
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"Early-onset Alzheimer's disease caused by mutations at codon 717 of the beta-amyloid precursor protein gene". Nature. 353: 844- ... 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: 704- ...
"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 ...
"Genetic cathepsin B deficiency reduces beta-amyloid in transgenic mice expressing human wild-type amyloid precursor protein". ... beta-secretase site of the amyloid precursor protein". The Journal of Biological Chemistry. 283 (12): 7745-53. doi:10.1074/jbc. ... animal model expressing human amyloid precursor protein (APP) containing the wild-type beta-secretase site sequence found in ... Klein DM, Felsenstein KM, Brenneman DE (March 2009). "Cathepsins B and L differentially regulate amyloid precursor protein ...
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
... 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 ...
"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. ...
P-glycoprotein efflux and other factors limit brain amyloid beta reduction by beta-site amyloid precursor protein-cleaving ... P-glycoprotein efflux and other factors limit brain amyloid beta reduction by beta-site amyloid precursor protein-cleaving ... P-glycoprotein efflux and other factors limit brain amyloid beta reduction by beta-site amyloid precursor protein-cleaving ... Based on this hypothesis, beta-site amyloid precursor protein (APP)-cleaving enzyme 1 (BACE1) inhibitors are an attractive ...
Aβ is cleaved from the β-amyloid precursor protein (AβPP) by β-secretase and γ-secretase. Heterogeneity of the C-terminal is ... Beta amyloid is focally deposited within the outer basement membrane in the amyloid angiopathy of Alzheimers disease. An ... seven amyloid proteins have been reported in CAA including amyloid β-protein (Aβ), cystatin C (ACys), prion protein (APrP), ... Some mutations in the amyloid β-protein precursor (AβPP) and presenilin genes are associated with severe CAA [see review5]. ...
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 ...
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 ...
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 ...
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. ... Amyloid Precursor Protein Secretases (beta-Secretase). Subscribe to New Research on Amyloid Precursor Protein Secretases ... beta-Secretase; alpha-Secretase; gamma-Secretase; Secretase; APP Secretase; Amyloid Precursor Protein Secretase; Secretases; ...
Amyloid beta (A4) precursor protein degradation products. Debate and discussion of any biological questions not pertaining to a ... Amyloid beta (A4) precursor protein degradation products of the pathogenic role of Alzheimers disease research progress. APP ... Cutting followed by the β and γ-secretase enzyme, resulting in extracellular s APP beta, A beta (A beta 40 and A beta 42) ... resulting in excess of A beta 40 and A beta 42, the formation of A beta deposition as the core of senile plaques and disease. ...
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 ...
A critical function for beta-amyloid precursor protein in neuronal migration revealed by in utero RNA interference. Young- ... AAV Data Hub Beta Open collection of AAV data generously shared by scientists ...
cerebrospinal fluid, beta-amyloid, apolipoprotein E, Alzheimers disease, amyloid precursor protein, ELISA, mild cognitive ... Measurement of alpha- and beta-secretase cleaved amyloid precursor protein in cerebrospinal fluid from Alzheimer patients. ... is redundant senile plaques mainly composed of beta-amyloid (Abeta) aggregates. Alternative cleavage of the amyloid precursor ... is redundant senile plaques mainly composed of beta-amyloid (Abeta) aggregates. Alternative cleavage of the amyloid precursor ...
Synthetic Human Amyloid beta (A4) Precursor Protein (aa 737-751)(CT) Blocking Peptide ... Synthetic Human Amyloid beta (A4) Precursor Protein (aa 737-751)(CT) Blocking Peptide. ...
Conclusions: : Both amyloid-beta (AB) and amyloid precursor protein (APP) appear to be present in AD and normal optic nerves ... Immunohistochemical Identification of Amyloid-Beta and Amyloid Precursor Protein in Alzheimers Disease Optic Nerve and Retina ... Immunohistochemical Identification of Amyloid-Beta and Amyloid Precursor Protein in Alzheimers Disease Optic Nerve and Retina ... D. Aggarwal, F. N. Ross-Cisneros, A. A. Sadun; Immunohistochemical Identification of Amyloid-Beta and Amyloid Precursor Protein ...
Synthetic Human Amyloid beta (A4) Precursor Protein A beta NT (aa 653-662) Peptide ... Synthetic Human Amyloid beta (A4) Precursor Protein A beta NT (aa 653-662) Peptide. ...
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. ...
... precursor protein (APP), transcript variant 5 as transfection-ready DNA - 10 µg - OriGene - cdna clones ... Myc-DDK-tagged ORF clone of Homo sapiens amyloid beta (A4) ... Myc-DDK-tagged ORF clone of Homo sapiens amyloid beta (A4) ... home , products , origene , myc-ddk-tagged orf clone of homo sapiens amyloid beta (a4) precursor protein (app), transcript ... Myc-DDK-tagged ORF clone of Homo sapiens amyloid beta (A4) precursor protein (APP), transcript variant 5 as transfection-ready ...
PeptidesAbetaBACE1AccumulationSenile plaquesAlzheimerAntibodiesDegradationCleavage of amyloidFragmentsSoluble1995AntibodyFragmentSAPPMutationAbnormalProteolysisPathwaysSequential cleavageCerebrospinalReduces amyloidBrainsPathologicalMoleculeInteractsProteolyticSecretionExpressionAlpha-secretaseBuildupMRNAPlaques in specificIntracellular domainInhibitorPathwaySelectiveVascularFingerprint
- 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)
- 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)
- 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)
- 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)
- 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)
- Prion diseases are neurodegenerative disorders which are caused by an accumulation of the abnormal, misfolded prion protein known as scrapie prion protein (PrP Sc ). (biomedcentral.com)
- One of the key features of Alzheimer's disease is the production and accumulation of the protein fragment beta-amyloid. (alz.org)
- Interrelation of inflammation and APP in sIBM: IL-1 beta induces accumulation of beta-amyloid in skeletal muscle. (medscape.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)
- Fe65 is an adaptor protein involved in both processing and signaling of the Alzheimer-associated amyloid-beta precursor protein, APP. (diva-portal.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)
- Beta-amyloid, in various forms, is toxic to nerve cells and it can aggregate into amyloid plaques, one of the hallmarks of Alzheimer pathology. (alz.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)
- Search, Find and Buy Antibodies, ELISA Kits and Proteins. (antibodies-online.com)
- 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)
- 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)
- Evidence for a nonsecretory, acidic degradation pathway for amyloid precursor protein in 293 cells," J. Biol. (patentgenius.com)
- Secretase Cleavage of Amyloid Precursor Protein," J. Of Biological Chem. (patentgenius.com)
- The mechanical stability of individual protein fragments are checked by laterally manipulating them with the STM tip. (aps.org)
- When these protein fragments are released from the cell, they can accumulate in the brain and form clumps called amyloid plaques. (medlineplus.gov)
- One of the fragments produced in this cutting process is β-amyloid. (wikipedia.org)
- The invention provides an antibody or antigen binding fragments thereof that binds to 3pE A.beta. (patents.com)
- Beta-amyloid is produced when its parent molecule, amyloid precursor protein (APP), is cut into fragments. (alz.org)
- amyloid precursor protein c-terminal fragments and the generation of amyloid .beta. (patentgenius.com)
- Cellular Actions of Beta-amyloid Precursor Protein and Its Soluble and Fibrillogenic Derivatives. (google.com)
- 1995. beta-Amyloid precursor protein-deficient mice show reactive gliosis and decreased locomotor activity. (jax.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)
- Antibody cross-linking dramatically increased production of A beta in a cholesterol-dependent manner. (uni-muenchen.de)
- Human amyloid related protein monoclonal antibody. (freepatentsonline.com)
- 1. An isolated antibody or antigen binding fragment thereof which binds to 3pE A.beta. (patents.com)
- assess the possibility of evaluating male infertility via screening for anti-sperm antibody (ASA) using protein biochips. (portlandpress.com)
- 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)
- 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)
- Here we report that cultured cells which express a beta-APP complementary DNA bearing a double mutation (Lys to Asn at residue 595 plus Met to Leu at position 596) found in a Swedish FAD family produce approximately 6-8-fold more A beta than cells expressing normal beta-APP. (nih.gov)
- 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, (thefreelibrary.com)
- The most common APP mutation changes one of the protein building blocks (amino acids) in the amyloid precursor protein. (medlineplus.gov)
- This mutation replaces the amino acid valine with the amino acid isoleucine at protein position 717 (written as Val717Ile or V717I). (medlineplus.gov)
- [ 72 ] Finally, recent research on patients with mild closed head injuries has found that although increased glial fibrillary acid protein (GFAP) levels correlated with abnormal neuroimaging, both GFAP and S100B failed to significantly correlate with clinical outcomes. (medscape.com)
- 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)
- 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)
- 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)
- Among its related pathways are Protein-protein interactions at synapses and Transmission across Chemical Synapses . (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)
- We illustrate its use in exploring protein aggregation in neurodegenerative disease and in the expansion of pathways associated to colon cancer. (biomedcentral.com)
- In these studies we utilize we use biochemical, molecular, and cell biological methods to characterize the role of these proteins in signal transduction pathways in striatal neurons. (yale.edu)
- Aβ is generated by sequential cleavage of the amyloid-β precursor protein (APP) by β- and then γ-secretase. (diva-portal.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)
- Moreover, HT reduces amyloid plaque deposition by regulating α-secretase and γ-secretase levels. (biomedcentral.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)
- Here we show the presence of misfolded prion protein (PrP(Sc)-like) in extracts of various sections of the brains of two SIDS victims. (biomedsearch.com)
- 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)
- APPBP2 interacts with microtubules and is functionally associated with beta-amyloid precursor. (biomol.com)
- 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)
- Facile and Sensitive Assay for Monitoring Proteolytic Activities with Defined Specificities: Studies on Amyloid .beta. (patentgenius.com)
- We investigate how ICT affects secretion of amyloid precursor protein (APP). (peerj.com)
- 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)
- 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)
- A beta generation was dependent on endocytosis and was reduced after expression of the dynamin mutant K44A and the Rab5 GTPase-activating protein, RN-tre. (uni-muenchen.de)
- Moreover, eASN upregulated expression of Sirt3 and Sirt5 , but downregulated of Sirt1 , which plays an important role in cell metabolism including Aβ precursor protein (APP) processing. (springer.com)
- Moreover, higher expression of pro-apoptotic protein Bax and enhancement of apoptotic cells' death were observed. (springer.com)
- Transcription is the first step in protein expression and the major point of regulation of the components that determine the characteristics, fate and functions of cells. (mdpi.com)
- Though translation of the mRNA message, as well as modification and correct folding of the polypeptide chains are essential for the protein composition of a cell, expression of all the components begins by transcription from DNA. (mdpi.com)
- 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)
- 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)
- Mus musculus amyloid beta (A4) precursor protein (App), transcript variant 1, mRNA. (jax.org)
- AD is characterized by the presence of neurofibrillary tangles and amyloid-containing plaques in specific regions of the brain. (elsevier.com)
- Amyloid plaques in specific parts of the brain can interfere with brain function, leading to seizures, movement problems, and other neurological features in some people with hereditary cerebral amyloid angiopathy. (medlineplus.gov)
- Adapter protein that forms a transcriptionally active complex with the gamma-secretase-derived amyloid precursor protein (APP) intracellular domain. (uniprot.org)
- This increase is augmented by simultaneous treatment with the protein phosphatase inhibitor okadaic acid. (pnas.org)
- ARPP-16 Is a Striatal-Enriched Inhibitor of Protein Phosphatase 2A Regulated by Microtubule-Associated Serine/Threonine Kinase 3 (Mast 3 Kinase). (yale.edu)
- We constructed a novel series of recombinant anticoagulant fusion proteins by linking annexin V (ANV), a PS-binding protein, to the Kunitz-type protease inhibitor (KPI) domain of tick anticoagulant protein, an aprotinin mutant ( 6L15 ), amyloid β-protein precursor, or tissue factor pathway inhibitor. (bloodjournal.org)
- The resulting ANV-KPI fusion proteins were 6- to 86-fold more active than recombinant tissue factor pathway inhibitor and tick anticoagulant protein in an in vitro tissue factor-initiated clotting assay. (bloodjournal.org)
- Α-secretase pathway: (1), also known as non-amyloid formation routes. (biology-online.org)
- 2) β-secretase pathway: also known as amyloid formation routes. (biology-online.org)
- 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)
- The encoded protein is a negative regulator of the Wnt signaling pathway. (wikipedia.org)
- Beta secretase 1-dependent amyloid precursor protein processing promotes excessive vascular sprouting through NOTCH3 signalling. (babraham.ac.uk)
- Fingerprint Dive into the research topics of 'Glutamate, beta-amyloid precursor proteins, and calcium mediated neurofibrillary degeneration. (elsevier.com)