• The genetic study showed promising results in "silencing" the genes that translate into tau protein, the primary component behind dementia. (medicaldaily.com)
  • Familial AD (FAD) cases are caused by autosomal dominant mutations in the genes for amyloid precursor protein (APP) and the presenilins (PS1 and PS2) ( Sisodia and St George-Hyslop, 2002 ). (jneurosci.org)
  • The first milestone with linkage analysis revealed the mutations in APP, PSEN1, and PSEN2 genes that cause EOAD. (oncotarget.com)
  • But pathogenic mutations in these three genes can only explain a small fraction of EOAD families. (oncotarget.com)
  • The most common cause of familial Alzheimer's disease is mutation of the genes encoding presenilins 1 and 2, which alters gamma-secretase activity to increase the production of the highly amyloidogenic Abeta42 isoform. (scienceopen.com)
  • Dominant mutations have been identified, in the beta-amyloid precursor protein gene (APP), and in two homologous genes presenilin 1 (PSEN-1) and presenilin 2 (PSEN-2). (ox.ac.uk)
  • Familial AD is the result of autosomal dominant mutations in one of three genes, amyloid precursor protein (APP), presenilin 1 (PSEN1), or presenilin 2 (PSEN2). (columbia.edu)
  • Sporadic AD patients harbor no mutations in APP, PSEN1, or PSEN2, but rather inherit mutations in other genes which do not guarantee the development of the disease, but are instead considered risk factors. (columbia.edu)
  • For the most part, in this way we identified a series of protein-non-coding genes, but also some protein-coding ones. (vechnayamolodost.ru)
  • Subsequently, the team was able to demonstrate how the mutant genes diminish alpha-secretase activity and led to increased levels of beta-amyloid, the main component of senile plaques in Alzheimer's disease. (curealz.org)
  • These findings are the first to document novel Alzheimer's gene mutations in animal models since the mutations in the original four Alzheimer's genes - APP, PSEN1 , PSEN2 , and APOE - were discovered in the 1990's. (curealz.org)
  • We published mutations (TREM2, ABCA7) and described an association (CD33) of microglia- and BBB-related genes that confer a risk for LOAD. (uniklinikum-jena.de)
  • There was no family history of AD, CJD, or any other neurological disease, and genetic analysis showed no disease specific mutations of the prion protein, presenilin 1 and 2, or amyloid precursor protein genes. (bmj.com)
  • Mutations in genes for the amyloid precursor protein, presenilin I, and presenilin II may lead to autosomal dominant forms of Alzheimer disease, typically with early onset. (msdmanuals.com)
  • 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)
  • These and other data suggest that A beta production begins with cleavage of beta APP by a still unknown protease(s) (beta-secretase[s]) at the met-asp bond proceeding the A beta N-terminus and that this occurs in part in early endosomes. (uni-muenchen.de)
  • The production of amyloid beta (Aβ) takes place by the proteolytic cleavage of beta-secretase protein on amyloid precursor protein (APP) whereas in AD, a pathogenic mutations affects the protease cleavage sites in APP and aid its cleavage [ 5 ]. (biomedcentral.com)
  • Plaques of beta-amyloid (Aβ) peptide, a cleavage product of the transmembrane protein, amyloid precursor protein (APP), accumulate in the extracellular spaces of the brain. (frontiersin.org)
  • Aβ is produced through the endoproteolysis of APP, a large type 1 transmembrane protein. (jneurosci.org)
  • While cross-correction, either upon secretion- recapture after bone marrow transplantation was shown in several lysosomal storage disorders caused by defective soluble hydrolases, our study is the first demonstration of cross-correction in the context of a lysosomal transmembrane protein and of TNTs as key cellular device in the transfer. (ucsd.edu)
  • APP 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)
  • APP is the protein from which amyloid-beta, the component of amyloid plaques, is cleaved. (columbia.edu)
  • A hallmark of Alzheimer's disease is the brain deposition of amyloid beta (Aβ), a peptide of 36-43 amino acids that is likely a primary driver of neurodegeneration. (rcsb.org)
  • All recognized mutations for AD are associated with increased deposition of amyloid-beta (Abeta), a peptide fragment comprising 39-43 amino acids that derive from the catabolism of the amyloid precursor protein (APP) molecule. (medscape.com)
  • Alzheimer's disease (AD) is a progressive neurodegenerative disorder that accounts for the most cases of dementia, which is characterized by the deposition of dense plaques of amyloid beta (Aβ) plaques and neurofibrillary tangles consisting of hyperphosphorylated tau. (oncotarget.com)
  • The major pathological hallmarks of AD include widespread neuronal and synaptic loss, excessive presence of astrocytes, and aggregation of multiple proteinaceous deposits for instance β-amyloid plaques and neurofibrillary tangles (NFT) [ 2 ]. (biomedcentral.com)
  • Carriers of this mutation develop a severe hereditary form of cerebral amyloid angiopathy (CAA), known as hereditary cerebral hemorrhage with amyloidosis, Dutch type (HCHWA-D). This disease is associated with recurrent strokes during the fifth and sixth decades of life often causing focal neurological symptoms and signs, including focal seizures. (alzforum.org)
  • Sequencing of exons 16 and 17 of the β-amyloid precursor protein gene (the exons which encode the β-amyloid fragment) in pedigree FAD4 revealed them to be of normal sequence. (mssm.edu)
  • Previous studies in the literature have resulted in conflicting reports on the potential neurotoxicity of the beta-cleaved Alzheimer's disease C-terminal fragment (beta-CTF) of beta-amyloid precursor protein in vivo. (amsterdamumc.org)
  • The amyloid beta-protein (A beta) is a proteolytic fragment of the beta-amyloid precursor protein (beta APP). (uni-muenchen.de)
  • This transgenic mouse model carries M233T/L235P knocked-in mutations in presenilin-1 and overexpresses mutated human beta-amyloid (Abeta) precursor protein. (uea.ac.uk)
  • Proteolytic processing of beta-CTF released Abeta. (amsterdamumc.org)
  • Accumulation of the amyloid-beta protein (Abeta) in the cerebral cortex is an early and invariant event in the pathogenesis of Alzheimer's disease. (scienceopen.com)
  • The final step in the generation of Abeta from the beta-amyloid precursor protein is an apparently intramembranous proteolysis by the elusive gamma-secretase(s). (scienceopen.com)
  • Here we report that mutation of either of two conserved transmembrane (TM) aspartate residues in presenilin-1, Asp 257 (in TM6) and Asp 385 (in TM7), substantially reduces Abeta production and increases the amounts of the carboxy-terminal fragments of beta-amyloid precursor protein that are the substrates of gamma-secretase. (scienceopen.com)
  • It is cleaved by AMYLOID PRECURSOR PROTEIN SECRETASES to produce peptides of varying amino acid lengths. (curehunter.com)
  • A 39-42 amino acid peptide, AMYLOID BETA-PEPTIDES is a principal component of the extracellular amyloid in SENILE PLAQUES. (curehunter.com)
  • AD is pathologically characterized by the deposition of pathogenic Aβ peptides that are derived from larger integral membrane proteins, termed β-amyloid precursor proteins (APPs). (jneurosci.org)
  • The amyloid precursor protein (APP) plays a central role in the pathophysiology of Alzheimer's disease in large part due to the sequential proteolytic cleavages that result in the generation of β-amyloid peptides (Aβ). (scienceopen.com)
  • We previously reported the constitutive secretion of A beta peptides from a variety of cells expressing beta APP under normal culture conditions. (uni-muenchen.de)
  • These endogenously produced A beta peptides have heterogeneous N- and C-termini that vary as a function of beta APP missense mutations. (uni-muenchen.de)
  • Expression of beta APP with various deletions of the cytoplasmic domain, including the NPTY motif, leads to decreased internalization and an associated decrease in the production of A beta peptides that begin at the usual asp1 start site. (uni-muenchen.de)
  • or = 10-20% of their secreted A beta peptides into SDS-stable dimers, trimers and sometimes tetramers under normal culture conditions. (uni-muenchen.de)
  • Polymorphisms that slightly vary native peptides or inflammatory processes set the stage for abnormal protein folding and amyloid fibril deposition. (medscape.com)
  • homozygous for the Psen1 mutation and homozygous for the co-injected APPSwe and tauP301L transgenes (Tg(APPSwe,tauP301L)1Lfa)) are viable, fertile and display no initial gross physical or behavioral abnormalities. (mmrrc.org)
  • Fibroblasts from familial AD patients, which contained mutations in APP, PSEN1 or PSEN2, showed a marked increase in MAM activity when compared to that of age-matched controls. (columbia.edu)
  • Amond them, the A21G Flemish mutation is unique as it shows a low tendency to aggregation, while deposits progressively appear in the vessel walls. (anaspec.com)
  • Cells secreting A beta may also be useful for examining the critical issue of the aggregation of A beta into its neurotoxic polymeric form under physiological conditions. (uni-muenchen.de)
  • Using this endogenous A beta aggregating system, we have begun to examine variables that influence aggregation and compounds which may retard it. (uni-muenchen.de)
  • In conclusion, studies of the regulation of A beta production and aggregation in cell culture can provide information under physiological conditions that can complement analyses of these processes in vivo. (uni-muenchen.de)
  • It is a chronic neurodegenerative disease caused by defected folding and aggregation of amyloid beta (Aβ) protein. (biomedcentral.com)
  • Although Aβ40 is several-fold more abundant in the brain Aβ42 is the major and sometimes exclusive component in amyloid plaques, due to its more aggregation prone nature [ 7 ]. (biomedcentral.com)
  • Signatures of type-I IFN-driven gene expression, and type-I IFNs themselves, are observed in the central nervous system during neurodegenerative diseases including Alzheimer's disease and other tauopathies, the umbrella term for diseases that feature aggregation of the cytosolic protein tau. (frontiersin.org)
  • Given the involvement of type-I IFNs in other neurogenerative diseases, we draw comparisons with other categories of homotypic protein aggregation. (frontiersin.org)
  • Only 10% of amyloidosis deposits consist of components such as glycosaminoglycans (GAGs), apolipoprotein-E (apoE), and serum amyloid P-component (SAP), while nearly 90% of the deposits consist of amyloid fibrils that are formed by the aggregation of misfolded proteins. (medscape.com)
  • The extracellular E2 domain, a dimeric coiled coil and one of the most highly conserved regions of the protein from Drosophila to humans. (handwiki.org)
  • [ 4 ] In humans, about 23 different unrelated proteins are known to form amyloid fibrils in vivo. (medscape.com)
  • Surprisingly, we found Alzheimer-type senile plaques and cerebral amyloid angiopathy in widespread areas of the brain. (bmj.com)
  • beta-amyloid is the main component of neuritic (senile) plaques, which consist of degenerated axonal or dendritic processes, astrocytes, and glial cells around an amyloid core. (msdmanuals.com)
  • Screening for the APP717 mutation in 5 further families with early onset Alzheimer's disease failed to reveal further cases with this variant. (mssm.edu)
  • The increased Aβ42/Aβ40 ratio is closely related to presenilin mutations correlating to early onset of AD [ 7 ]. (biomedcentral.com)
  • If we can find or develop a drug to safely increase alpha-secretase activity," said Tanzi, "that would decrease the accumulation of beta-amyloid plaques and slow down or even stop the onset of the disease. (curealz.org)
  • 2010. Adeno-associated virus gene therapy with cholesterol 24-hydroxylase reduces the amyloid pathology before or after the onset of amyloid plaques in mouse models of Alzheimer's disease. (ocl-journal.org)
  • The latter alteration was similar to that observed in presymptomatic transgenic mice carrying the E693 mutation. (alzforum.org)
  • To readdress this question by rigorous quantitative methods, we analyzed transgenic mice expressing human beta-CTF with the I45F mutation (SPA4CT) under control of the prion protein promoter by stereological techniques. (amsterdamumc.org)
  • 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)
  • The histological manifestation of AD presents extracellular deposits of β-amyloid peptide (Aβ) and the intracellular formation of neurofibrillary tangles consisting of paired helical filaments of hyperphosphorylated tau protein [ 4 ] [ 5 ] . (encyclopedia.pub)
  • Lysosomes are mainly involved in the degradation of extracellular material that enter the cell by endocytosis but are also involved in the homeostasis of other organelles and cellular proteins, including mitophagic and autophagic processes in an age dependent manner. (uniklinikum-jena.de)
  • Amyloidosis is a clinical disorder caused by extracellular and/or intracellular deposition of insoluble abnormal amyloid fibrils that alter the normal function of tissues. (medscape.com)
  • Several mutations in the beta amyloid precursor gene cause autosomal dominant Alzheimer's Disease in a number of kindreds. (anaspec.com)
  • Accordingly, our laboratory has developed small molecule p75 NTR ligands that increase survival signaling and inhibit amyloid-β-induced degenerative signaling in in vitro studies. (plos.org)
  • The presenilins constitute the enzymatic core of the γ-secretase complex, which cleaves amyloid-beta from a precursor APP molecule. (columbia.edu)
  • To investigate the APP in vivo interactome in an unbiased manner, we generated mice that harbor a mouse prion protein promoter-driven cDNA encoding human APP-695 fused to a C-terminal affinity tag. (jneurosci.org)
  • Immunohistochemistry showed widespread cortical depositions of disease associated prion protein (PrP sc ) in a synaptic pattern, and western blot analysis identified PrP sc of type 2A according to Parchi et al . (bmj.com)
  • In addition, fibrillar and hyperphosphorylated assemblies of the microtubule-associated protein tau accumulate in the cytoplasm of neurons ( Goedert and Spillantini, 2006 ). (frontiersin.org)
  • All types of amyloid consist of one major fibrillar protein that defines the type of amyloid. (medscape.com)
  • [ 2 ] Enterokinase, also known as enteropeptidase, is a key enzyme for intestinal digestion of proteins. (medscape.com)
  • The groups used very different isolation methods (i.e., expression cloning, protein purification, genomics), yet all identified the same enzyme and concurred that it possessed all the known characteristics of β-secretase ( Fig. 1 ) ( Cole and Vassar, 2008 ). (jneurosci.org)
  • Tanzi's research suggests that the ADAM10 gene makes an enzyme called alpha-secretase, which cleaves the Amyloid Precursor Protein (APP) to prevent the formation of beta-amyloid, the toxic protein that triggers brain pathology in Alzheimer's disease. (curealz.org)
  • This mutation results in the accumulation of Aβ in cerebral vessel walls which is associated with cell death and loss of vessel wall integrity. (alzforum.org)
  • This mutation causes increased accumulation of amyloid-beta protein in the walls of cerebral arteries and capillaries. (nictiz.nl)
  • Mutations in the CTNS gene, encoding a lysosomal cystine transporter, lead to cystine accumulation and multi-organ failure such as end stage renal failure, blindness, myopathy, diabetes and central nervous system defects. (ucsd.edu)
  • In Alzheimer's disease, the trigger protein is amyloid beta (Aß), a polypeptide of 37-49 amino acids, which is generated by proteolysis from the Amyloid-beta precursor protein (APP). (uniklinikum-jena.de)
  • Many mechanisms of protein function contribute to amyloidogenesis, including "nonphysiologic proteolysis, defective or absent physiologic proteolysis, mutations involving changes in thermodynamic or kinetic properties, and pathways that are yet to be defined. (medscape.com)
  • In an attempt to understand the function of APP, in vitro studies have focused on the identification of interacting proteins. (jneurosci.org)
  • Using an in vitro system, we demonstrate that neuroligin-1 and -2, postsynaptically localized proteins, can trigger the de novo formation of presynaptic structure. (scienceopen.com)
  • Axonal amyloid precursor protein expressed by neurons in vitro is present in a membrane fraction with caveolae-like properties. (ocl-journal.org)
  • Most forms of HCHWA (Dutch, Arctic, Piedmont, Iowa, Flemish and Italian) are due to a point-mutation in the APP gene on chromosome 21q21.2, which encodes the beta-amyloid precursor protein. (nictiz.nl)
  • Only one form of HCHWA, Icelandic type, is due to a mutation in the CST3 gene on chromosome 20p11.2, encoding the precursor protein cystatin C. (nictiz.nl)
  • [ 4 ] Beta-site APP-cleaving enzyme1 (BACE1), a protease that has been closely linked to the pathogenesis of Alzheimer disease but highly expressed in pancreatic acinar cells, could possibly protect the pancreas from premature trypsinogen activation. (medscape.com)
  • Alzheimer disease causes progressive cognitive deterioration and is characterized by beta-amyloid deposits and neurofibrillary tangles in the cerebral cortex and subcortical gray matter. (msdmanuals.com)
  • FANCC is one of many Fanconi anemia (FA) proteins that act in signaling events following cellular stress including DNA damage and oxidative stress. (biomedcentral.com)
  • The number of hypotheses are proposed along the years to describe the root cause of AD such as the production of β-amyloid, cholinergic hypothesis, excitotoxicity and oxidative stress hypothesis [ 3 ] as summarized in Fig. 1 . (biomedcentral.com)
  • 2000. Endocytic pathway abnormalities precede amyloid beta deposition in sporadic Alzheimer's disease and Down syndrome: differential effects of APOE genotype and presenilin mutations. (ocl-journal.org)
  • In addition, the brain deposits are prefereably composed of A-beta 1-40 rather than A beta 1-42, in opposition to the other familial AD. (anaspec.com)
  • Plaque-type and vascular amyloid was immunohistochemically identified as deposits of beta-A4 peptide. (bmj.com)
  • Various descriptive classification systems were proposed based on the organ distribution of amyloid deposits and clinical findings. (medscape.com)
  • 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)
  • Furthermore, the effects in mouse brains strongly suggest that diminished alpha-secretase activity owing to the ADAM10 gene mutations causes Alzheimer's and therefore support ADAM10 as a promising therapeutic target for the treatment and prevention of the disease. (curealz.org)
  • Aβ is liberated from type I integral membrane proteins, termed β-amyloid precursor proteins (APPs), by the concerted action of β-secretase (BACE1) and γ-secretase (for review, see Selkoe, 2002 ). (jneurosci.org)
  • 2017. Lack of BACE1 S-palmitoylation reduces amyloid burden and mitigates memory deficits in transgenic mouse models of Alzheimer's disease. (ocl-journal.org)
  • Ala mutation still inhibited gamma-secretase activity. (scienceopen.com)
  • Analogous mutagenesis experiments around the A beta C-terminus revealed that the unknown protease(s) cleaving here ("gamma-secretase[s]") does not show such specificity. (uni-muenchen.de)
  • Several non-synonymous point mutations in MAPT , the gene that encodes tau, give rise to familial inherited tauopathies such as frontotemporal lobar degeneration with tau-immunoreactive inclusions (FTLD-tau) ( Goedert, 2018 ). (frontiersin.org)
  • To characterize the substrate requirements of beta-secretase, beta APP was mutagenized by placing stop codons within or at the end of the transmembrane domain or substituting other amino acids for the wild-type met and asp at the P1 and P1' positions. (uni-muenchen.de)
  • 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)
  • A mutation (A673T) in the APP gene protects against Alzheimer's disease. (wikipedia.org)
  • Alzheimer's disease and the beta amyloid gene. (ox.ac.uk)
  • These data implicate that expression of beta-CTF per se is not neurotoxic, and that other mechanisms are responsible for the neurotoxic events in Alzheimer's disease brain. (amsterdamumc.org)
  • The β-amyloid (Aβ) peptide is the major constituent of amyloid plaques in Alzheimer's disease (AD) brain and is likely to play a central role in the pathogenesis of this devastating neurodegenerative disorder. (jneurosci.org)
  • This new landmark genetic discovery by Rudy Tanzi, who is also Research Consortium Chair at Cure Alzheimer's Fund, further buttress the widely-held "Amyloid Hypothesis" and suggest specific new therapeutic approaches to stopping Alzheimer's disease. (curealz.org)
  • 2018. Cognitive and neuroimaging features and brain beta-amyloidosis in individuals at risk of Alzheimer's disease (INSIGHT-preAD): a longitudinal observational study. (ocl-journal.org)
  • For example, several mutations outside the Aβ region associated with familial Alzheimer's have been found to dramatically increase production of Aβ. (wikipedia.org)
  • Describes a group of rare familial central nervous system disorders characterized by amyloid deposition in the cerebral blood vessels leading to hemorrhagic and non-hemorrhagic strokes, focal neurological deficits, and progressive cognitive decline eventually leading to dementia. (nictiz.nl)
  • While the effect of familial AD mutations on MAM has been characterized, the mechanism of mitochondrial dysfunction seen in the more common sporadic form of the disease remains obscure. (columbia.edu)
  • Moreover, when crossed to a mouse model of AD expressing a mutant amyloid precursor protein, brains of these mice showed neuronal degeneration and early and robust formation of tangle-like structures containing P-tau. (ox.ac.uk)
  • Amyloid-beta precursor protein (APP) is an integral membrane protein expressed in many tissues and concentrated in the synapses of neurons. (wikipedia.org)
  • The amyloid beta region of the protein, located in the membrane-spanning domain, is not well conserved across species and has no obvious connection with APP's native-state biological functions. (wikipedia.org)
  • A single-pass type I membrane protein. (curehunter.com)
  • Using this tag, we prepared mild detergent lysates from transgenic mouse brain cortical membrane preparations and isolated a number of previously identified APP-interacting proteins. (jneurosci.org)
  • The "amyloid cascade hypothesis" places Aβ pathology as an upstream, causative insult that unleashes a range of ensuing consequences including tau pathology and neurotoxicity ( Hardy and Higgins, 1992 ). (frontiersin.org)
  • Thus, this study demonstrates that using proteomic methods on our transgenic model can uncover important in vivo APP-interacting proteins that will provide insights into the biology of APP. (jneurosci.org)
  • Thus, this study demonstrates that our transgenic model can uncover important in vivo APP-interacting proteins that will contribute to our understanding of APP processing in in vivo settings. (jneurosci.org)
  • Here, we show that APP can coimmunoprecipitate NEEP21 from nontransgenic mouse brain and from mammalian cells stably coexpressing both proteins. (jneurosci.org)
  • Homologous proteins have been identified in other organisms such as Drosophila (fruit flies), C. elegans (roundworms), and all mammals. (wikipedia.org)
  • Mutation in the Drosophila TM2D3 homolog, almondex, causes a phenotype similar to loss of Notch/Presenilin signaling. (ox.ac.uk)
  • 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. (utsouthwestern.edu)
  • FANCC is a predominantly cytoplasmic protein that has multiple functions including DNA damage signaling, oxygen radical metabolism, signal transduction, transcriptional regulation and apoptosis. (biomedcentral.com)
  • In a previous report, we showed that the Fanconi anemia C protein, FANCC, interacts directly with UNC5A via its cytoplasmic death domain. (biomedcentral.com)
  • This subtype is due to a mutation in the APP gene (21q21.2), encoding the beta-amyloid precursor protein. (findzebra.com)
  • A progressive increase in amyloid beta peptide deposition is observed, with intracellular immunoreactivity being detected in some brain regions as early as 3-4 months. (mmrrc.org)
  • The addition of an affinity tag allowed us to avoid the use of antibodies targeted toward the intracellular C-terminal tail of APP, a region to which a number of reported interacting proteins bind ( King and Turner, 2004 ). (jneurosci.org)
  • 3 beta ( GSK-3β), N-methyl-D-aspartate (NMDA) receptor, monoamine oxidases (MAOs), metal ions in the brain, 5-hydroxytryptamine (5-HT) receptors, the third subtype of histamine receptor (H 3 receptor), to phosphodiesterases (PDEs), along with a summary of their respective relationship to the disease network. (encyclopedia.pub)
  • The Uncoordinated 5A (UNC5A) protein is part of a family of receptors that play roles in axonal pathfinding and cell migration. (biomedcentral.com)
  • In addition, UNC5 proteins have been proposed to function as 'dependence receptors', triggering apoptosis in the absence of the ligand Netrin-1 and sending survival signals when bound to the ligand [ 5 ]. (biomedcentral.com)
  • Treatment of A beta-secreting cells with agents that alter intravesicular pH showed that an acidic compartment is required for proper A beta generation. (uni-muenchen.de)
  • Immunolabeling of cell-surface beta APP in living neurons and non-neuronal cells directly demonstrated the endocytosis of the protein and its rapid recycling (within 5-10 minutes) to the cell surface, as well as the trafficking of some beta APP to lysosomes. (uni-muenchen.de)
  • Ubiquitination and autophagy target proteins via post-translational modifications for regulating the protein homeostasis of amyloid precursor protein (APP) and its harmful byproduct amyloid beta (Aβ) in neurons, but also in other cells of the neurovascular unit including the BBB. (uniklinikum-jena.de)
  • These proteins either arise from proteins expressed by cells at the deposition site (localized), or they precipitate systemically after production at a local site (systemic). (medscape.com)
  • Effects of atrial natriuretic peptide on protein kinase C activation, second messengers, and function in a human cell line. (pro-resurs.com)
  • Beta -amyloid may also alter kinase and phosphatase activities in ways that eventually lead to hyperphosphorylation of tau (a protein that stabilizes microtubules) and formation of neurofibrillary tangles. (msdmanuals.com)
  • Amyloid-beta precursor protein is an ancient and highly conserved protein. (wikipedia.org)
  • In Pick's disease (PiD), progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD), tau pathology is the main, often sole observed protein pathology ( Spillantini and Goedert, 2013 ). (frontiersin.org)