APBA2 (amyloid beta precursor protein binding family A member 2)
... , Authors: Dessen P. Published in: Atlas Genet Cytogenet Oncol Haematol.http://atlasgeneticsoncology.org/Genes/GC_APBA2.html
APBB1 (amyloid beta precursor protein binding family B member 1)
... , Authors: Dessen P. Published in: Atlas Genet Cytogenet Oncol Haematol.http://atlasgeneticsoncology.org/Genes/GC_APBB1.html
Trafficking of cell-surface amyloid beta-protein precursor. II. Endocytosis, recycling and lysosomal targeting detected by...
Amyloid beta-protein (A beta) is a proteolytic fragment of the amyloid beta-protein precursor (beta PP). Progressive cerebral deposition of A beta is an early and invariant feature of Alzheimer's disease. The cellular trafficking of beta PP is of particular interest because understanding the production of A beta requires a comprehensive elucidation of the metabolic pathways of this protein. In addition, beta PP is a type I integral membrane glycoprotein that belongs to a class of molecules with both full length and secreted products. Recent evidence suggests that beta PP can be processed in an endosomal/lysosomal pathway. In the latter organelles, a number of beta PP carboxy-terminal derivatives are found, but the precise ...http://jcs.biologists.org/content/109/5/999
MAPPING THE TRANSCRIPTIONAL REGULATORY NETWORK OF THE AMYLOID PRECURSOR PROTEIN INTRACELLULAR DOMAIN (AICD) | ScholarBank@NUS
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 ...http://scholarbank.nus.edu.sg/handle/10635/37860
Release of excess amyloid beta protein from a mutant amyloid beta protein precursor | Science
The 4-kilodalton amyloid beta protein (A beta), which forms fibrillar deposits in Alzheimer's disease (AD), is derived from a large protein referred to as the amyloid beta protein precursor (beta APP). Human neuroblastoma (M17) cells transfected with constructs expressing wild-type beta APP or a mutant, beta APP delta NL, recently linked to familial AD were compared. After continuous metabolic labeling for 8 hours, cells expressing beta APP delta NL had five times more of an A beta-bearing, carboxyl terminal, beta APP derivative than cells expressing wild-type beta APP and they released six times more A beta into the medium. Thus this mutant beta APP may cause AD because its processing is altered in a way ...http://science.sciencemag.org/content/259/5094/514
"Flavonoids as modulators of amyloid precursor protein metabolism and A" by Kavon Rezai-Zadeh
Alzheimer disease (AD) is a progressive neurodegenerative disorder pathologically characterized by deposition of ß-amyloid (Aß) peptides as plaques in the brain. Central to this AD pathology is mismetabolism of the amyloid precursor protein (APP). Recent studies suggest that flavonoids, a class of secondary plant metabolites, may be useful for the prevention and treatment of a variety of neurodegenerative diseases. The studies detailed herein, investigate the ability of two such classes of flavonoids, green tea derived catechins and 5,7-dihydroxyflavones, to modulate APP metabolism in 'Swedish' mutant APP (APP[subscript]sw) models of AD. Studies showed that green tea derived (-)-epigallocatechin-3-gallate (EGCG) effectively reduced Aß generation and resultant amyloidosis both in vitro and in vivo. In concert with these findings, EGCG markedly promoted non-amyloidogenic APP proteolysis via activation of the ...http://scholarcommons.usf.edu/etd/473/
Dynamics of β-Amyloid Reductions in Brain, Cerebrospinal Fluid, and Plasma of β-Amyloid Precursor Protein Transgenic Mice...
Handling of Mice. The Tg2576 mice were developed by Karen Hsaio (Hsiao et al., 1996) and licensed from the Mayo Foundation for Medical Education and Research (Rochester, MN). Male Tg2576 transgenic mice were bred to normal C57BL6/SJL females at the Bristol-Myers Squibb facility in Wallingford, CT. Mice were housed with a 6:00 AM to 6:00 PM light/dark cycle and allowed free access to food and water. Both male and female mice were used in these studies, and although no differences in Aβ were observed between them, only one sex was used in a single study. Young Tg2576 mice were used between 3 and 6 months of age, whereas aged animals were used at 14 to 17 months. BMS-299897 was synthesized by the Medicinal Chemistry groups of SIBIA Neurosciences, Inc. (now Merck Research Laboratories, San Diego, CA) and Bristol-Myers Squibb. Animals were dosed by oral gavage in a volume of 6 ml/kg in polyethylene glycol, average molecular weight of 400, or a vehicle consisting of 10% propylene glycol, 7.5% ...http://jpet.aspetjournals.org/content/312/2/635.long
Anti-Amyloid beta precursor protein抗体[Y188] (ab32136)
Amyloid beta precursor protein兔单克隆抗体可与小鼠, 大鼠, 人样本反应并经WB, IP, IHC,ICC, Flow Cyt实验严格验证，被21篇文献引用并得到5个独立的用户反馈。http://www.abcam.cn/amyloid-precursor-protein-antibody-y188-ab32136.html
Impairment of hippocampal gamma (γ)-frequency oscillations in vitro in mice overexpressing human amyloid precursor protein (APP...
Alzheimer's disease is associated with a dramatic decline in cognitive performance including hippocampal-dependent memory. We have investigated one feature of hippocampal activity related to memory, the γ (30-80 Hz)-frequency rhythm. Hippocampal slices from mice overexpressing the human amyloid precursor protein (APP)SWE mutation (TAS10) were compared at 8 and 16 months of age with wild-type littermates. In slices obtained from TAS10 mice aged 8 months the γ-frequency activity evoked with bath application of 200 nm kainate was significantly (P , 0.05; n = 8 slices, five animals) impaired (area power, 5956 ± 2487 µV2) compared to slices from wild-type animals (area power, 18 256 ± 7880 µV2). At 16 months of age there was no longer a significant difference (P , 0.05; n = 11 slices from five animals) between slices from TAS10 and wild-type control mice as the wild-type mice now exhibited a marked age-dependent reduction in γ-frequency activity (TAS10 area ...http://onlinelibrary.wiley.com/doi/10.1111/j.1460-9568.2007.05705.x/abstract
feh-1 and apl-1, the Caenorhabditis elegans orthologues of mammalian Fe65 and β-amyloid precursor protein genes, are involved...
In mammals, many of the proteins taking part in the complex network of interactions centred at the cytosolic domain of APP belong to gene families. This is in fact the case for APP-like genes, as well as for Fe65- and X11-like members. APP-like gene family members have been analysed in depth, in mammals, by reverse genetics. However, their redundancy prevented the generation of clear phenotypes from murine knock-outs of the single APP, APLP1 or APLP2 genes ( Zheng et al., 1995; von Koch et al., 1997; Heber et al., 2000), whereas mice with combined knock-outs displayed severe phenotypes, dying early and post-natally. Taken together, the functions of these genes have been proposed as essential and partially redundant in mammals ( Heber et al., 2000). A similar phenotype, although not strictly predictable, might occur if reverse genetic approaches were used with the mammalian Fe65 gene family members. This was one of the reasons that prompted us to investigate potential Fe65-like genes in the ...http://jcs.biologists.org/content/115/7/1411
ALZFORUM | NETWORKING FOR A CURE
Iijima K, Ando K, Takeda S, Satoh Y, Seki T, Itohara S, Greengard P, Kirino Y, Nairn AC, Suzuki T. Neuron-specific phosphorylation of Alzheimer's beta-amyloid precursor protein by cyclin-dependent kinase 5 ...http://www.alzforum.org/papers/neuron-specific-phosphorylation-alzheimers-beta-amyloid-precursor-protein-cyclin-dependent
APP (Amyloid Precursor Protein), eFluor 570, clone: 22C11, eBioscience™ 100μg; eFluor 570 APP (Amyloid Precursor Protein),...
APP (Amyloid Precursor Protein), eFluor 570, clone: 22C11, eBioscience™ 100μg; eFluor 570 APP (Amyloid Precursor Protein), eFluor 570, clone: 22C11,...https://www.fishersci.co.uk/shop/products/app-amyloid-precursor-protein-mouse-efluor-570-clone-22c11-ebioscience-2/15558956
FKBP12 regulates the localization and processing of amyloid precursor protein in human cell lines.
Liu F.L., Liu T.Y., Kung F.L.. One of the pathological hallmarks of Alzheimer's disease is the presence of insoluble extracellular amyloid plaques. These plaques are mainly constituted of amyloid beta peptide (A beta), a proteolytic product of amyloid precursor protein (APP). APP processing also generates the APP intracellular domain (AICD). We have previously demonstrated that AICD interacts with FKBP12, a peptidyl-prolyl cis-trans isomerase (PPIase) ubiquitous in nerve systems. This interaction was interfered by FK506, a clinically used immunosuppressant that has recently been reported to be neuroprotective. To elucidate the roles of FKBP12 in the pathogenesis of Alzheimer's disease, the effect of FKBP12 overexpression on APP processing was evaluated. Our results revealed that APP processing was shifted towards the amyloidogenic pathway, accompanied by a change in the ...http://www.uniprot.org/citations/24499793
L-APP - L-beta A4 amyloid precursor protein | AcronymAttic
How is L-beta A4 amyloid precursor protein abbreviated? L-APP stands for L-beta A4 amyloid precursor protein. L-APP is defined as L-beta A4 amyloid precursor protein rarely.https://www.acronymattic.com/L_beta-A4-amyloid-precursor-protein-
Novel mutations introduced at the β-site of amyloid β protein precursor enhance the production of amyloid β peptide by BACE1 in...
Abnormal production and accumulation of amyloid-β peptide (Aβ) plays a major role in the pathogenesis of Alzheimer's disease (AD). β-secretase (BACE1) is responsible for the cleavage at the β-site in amyloid β protein precursor (AβPP/APP) to generatehttps://content.iospress.com/articles/journal-of-alzheimers-disease/jad00409
The effects of Alzheimer's disease, other dementias, and premortem course on beta-amyloid precursor protein messenger RNA in...
There are conflicting data regarding alterations in beta-amyloid precursor protein (APP) mRNAs in Alzheimer's disease (AD). This may be due partly to variables such as agonal state and choice of control group. We have used in situ hybridization histochemistry to study expression of APP mRNAs, with and without the domain encoding the Kunitz protease inhibitor, in a way that overcomes some of the limitations of the current data. Tissue from frontal cortex was collected at rapid autopsy from patients with AD or other cognitive impairments whose terminal phase was prospectively assessed. There were three main findings. Firstly, the amount of APP mRNAs correlated strongly with glutamate decarboxylase activity and was reduced in association with terminal pyrexia. These correlations suggest that agonal state affects APP mRNA and, therefore, that differences in premortem course may contribute to the varying changes in APP transcript abundance ...https://www.psych.ox.ac.uk/publications/657637
Amyloid precursor protein mRNA levels in Alzheimer's disease brain
Insoluble beta-amyloid deposits in Alzheimer's 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 ...http://uu.diva-portal.org/smash/record.jsf?pid=diva2:100376
Antimicrobial activity of peptides derived from human ss-amyloid precursor protein
Antimicrobial peptides are important effector molecules of the innate immune system. Here, we describe that peptides derived from the heparin-binding disulfide-constrained loop region of human beta-amyloid precursor protein are antimicrobial. The peptides investigated were linear and cyclic forms of NWCKRGRKQCKTHPH (NWC15) as well as the cyclic form comprising the C-terminal hydrophobic amino acid extension FVIPY (NWCKRGRKQCKTHPHFVIPY; NWC20c). Compared with the benchmark antimicrobial peptide LL-37, these peptides efficiently killed the Gram-negative bacteria Escherichia coli and Pseudomonas aeruginosa, the Gram-positive Staphylococcus aureus and Bacillus subtilis, and the fungi Candida albicans and Candida parapsilosis. Correspondingly, fluorescence and electron microscopy demonstrated that the peptides caused defects in bacterial membranes. Analogously, the peptides permeabilised negatively charged liposomes. Despite their bactericidal ...http://uu.diva-portal.org/smash/record.jsf?pid=diva2:510960
Lack of Neurodegeneration in Transgenic Mice Overexpressing Mutant Amyloid Precursor Protein Is Associated with Increased...
We have shown that the expression of a number of protective genes and a protective pathway culminating in Bad phosphorylation are increased in mice that overexpress APPSw and have no neuronal loss. Increased levels of IGF-2 mRNA and protein correspond to increased activation of the IGF-1 receptor, activation of Akt and Erk1/2, and phosphorylation of Bad in APPSw mice. The increased expression of TTR and IGF-2 as well as increased phospho-Bad staining in hippocampal neurons was consistent in both preplaque (6 months) and postplaque (12 months) Tg2576 mice. Other conditions, such as the presence of a human tau gene, may be necessary for complete AD pathology. However, taken together, these data imply that the lack of neurodegeneration in APPSw mice is a result of the activation of known cell survival pathways associated with the overexpression of APPSw.. Transthyretin has been shown to bind Aβ and inhibit Aβ aggregation (Schwarzman et al., 1994). In human AD patients the ...http://www.jneurosci.org/content/22/17/7380.long
Imaging distinct conformational states of amyloid-β fibrils in Alzheimer's disease using novel luminescent probes
Using luminescent conjugated polyelectrolyte probes (LCPs), we demonstrate the possibility to distinguish amyloid-β 1-42 peptide (Aβ1-42) fibril conformations, by analyzing in vitro generated amyloid fibrils of Aβ1-42 formed under quiescent and agitated conditions. LCPs were then shown to resolve such conformational heterogeneity of amyloid deposits in vivo. A diversity of amyloid deposits depending upon morphology and anatomic location was illustrated with LCPs in frozen ex vivo brain sections from a transgenic mouse model (tg-APPswe) of Alzheimer's 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 ...http://liu.diva-portal.org/smash/record.jsf?pid=diva2:261471
Abstract: Amyloid beta protein precursor is phosphorylated by JNK-1 independent of, yet facilitated by, JNK interacting protein...
Alzheimer's Disease (AD) is genetically linked to the processing of amyloid b protein precursor (AbPP). Aside from being the precursor of the Amyloidhttp://www.prohealth.com/library/showarticle.cfm?libid=5470
Perturbations of the Straight Transmembrane alpha-Helical Structure of the Amyloid Precursor Protein Affect Its Processing by...
Background: Amyloid- neurotoxicity depends on the specificity of the proteolytic cleavage of the amyloid precursor protein (APP) transmembrane domain. Results: The APP transmembrane -helix is straight in a biological membrane bilayer. Conclusion: The flexibility of APP is key for adapting to the lipid environment and modulating proteolytic processing by -secretase. Significance: The dynamic characterization of APP is expected to rationalize the design of -secretase modulators. The amyloid precursor protein (APP) is a widely expressed type I transmembrane (TM) glycoprotein present at the neuronal synapse. The proteolytic cleavage by -secretase of its C-terminal fragment produces amyloid- (A) peptides of different lengths, the deposition of which is an early indicator of Alzheimer disease. At present, there is no consensus on the conformation ...https://infoscience.epfl.ch/record/199679
The Arctic mutation interferes with processing of the amyloid precursor protein
Alzheimer's disease (AD) is a progressive neurodegenerative disorder, neuropathologically characterized by neurofibrillay tangles and deposition of amyloid-β (Aβ) peptides. Several mutations in the gene for amyloid precursor protein (APP) cause familial AD and affect APP processing leading to increased levels of Aβ42. However, the Arctic Alzheimer mutation (APP E693G) reduces Aβ levels. Instead, the increased tendency of Arctic Aβ peptides to form Aβ protofibrils is thought to contribute to the pathogenesis.. In this thesis, the pathogenic mechanisms of the Arctic mutation were further investigated, specifically addressing if and how the mutation affects APP processing. Evidence of a shift towards β-secretase cleavage of Arctic APP was demonstrated. Arctic APP did not appear to be an inferior substrate for α-secretase, but the availability of Arctic APP for α-secretase cleavage was reduced, with diminished levels of cell surface APP in ...http://uu.diva-portal.org/smash/record.jsf?pid=diva2:169717
Amyloid Precursor Protein C term antibody available through Research Diagnostics Inc
The amyloid precursor protein (APP) is a large membrane protein whose C terminus projects into the extracellular space. In Alzheimer's disease (AD), the APP is proteolytically cleaved at the N-terminal of ABeta by Beta-secretase (BACE) to release a ~100 kD APPsbeta protein into the extracellular space. The remaining 12 kD fragment remains membrane bound where it can be cleaved at its C-terminus by ( -secretase (presenilins) to release the insoluble Abeta peptide into the extracellular space with the ~8 kD APP C-terminal fragment (CTFbeta) remaining membrane bound. The APP is the subject of intensive investigations to determine how this protein is broken down abnormally in AD brains to give rise to Abeta, which is present in senile plaques and vessels. ...http://researchd.com/neuroabs/amyprecabg.htm
Site-specific characterization of threonine, serine, and tyrosine glycosylations of amyloid precursor protein/amyloid beta...
Halim A., Brinkmalm G., Ruetschi U., Westman-Brinkmalm A., Portelius E., Zetterberg H., Blennow K., Larson G., Nilsson J.. The proteolytic processing of human amyloid precursor protein (APP) into shorter aggregating amyloid β (Aβ)-peptides, e.g., Aβ1-42, is considered a critical step in the pathogenesis of Alzheimer's disease (AD). Although APP is a well-known membrane glycoprotein carrying both N- and O-glycans, nothing is known about the occurrence of released APP/Aβ glycopeptides in cerebrospinal fluid (CSF). We used the 6E10 antibody and immunopurified Aβ peptides and glycopeptides from CSF samples and then liquid chromatography-tandem mass spectrometry for structural analysis using collision-induced dissociation and electron capture dissociation. In addition to 33 unglycosylated APP/Aβ peptides, we identified 37 APP/Aβ glycopeptides with sialylated core 1 like O-glycans attached to Thr(-39, -21, -20, and -13), in a ...http://www.uniprot.org/citations/21712440