App

Summary

Gene Symbol: App
Description: amyloid beta precursor protein
Alias: Abeta, amyloid-beta A4 protein, amyloid beta A4 protein, ABPP, alzheimer disease amyloid A4 protein homolog, amyloid A4, amyloid beta (A4) precursor protein, amyloid precursor protein, amyloidogenic glycoprotein, beta-amyloid precursor protein
Species: rat
Products:     App

Top Publications

  1. Kuperstein I, Broersen K, Benilova I, Rozenski J, Jonckheere W, Debulpaep M, et al. Neurotoxicity of Alzheimer's disease A? peptides is induced by small changes in the A?42 to A?40 ratio. EMBO J. 2010;29:3408-20 pubmed publisher
    ..Our work also suggests the dynamic nature of the equilibrium between toxic and non-toxic intermediates. ..
  2. Snyder E, Nong Y, Almeida C, Paul S, Moran T, Choi E, et al. Regulation of NMDA receptor trafficking by amyloid-beta. Nat Neurosci. 2005;8:1051-8 pubmed
    ..Dephosphorylation of the NMDA receptor subunit NR2B at Tyr1472 correlated with receptor endocytosis. These data indicate a new mechanism by which amyloid-beta can cause synaptic dysfunction and contribute to Alzheimer disease pathology. ..
  3. Ho A, Sudhof T. Binding of F-spondin to amyloid-beta precursor protein: a candidate amyloid-beta precursor protein ligand that modulates amyloid-beta precursor protein cleavage. Proc Natl Acad Sci U S A. 2004;101:2548-53 pubmed
    Amyloid-beta precursor protein (APP), a type I membrane protein, is physiologically processed by alpha- or beta-secretases that cleave APP N-terminal to the transmembrane region...
  4. Magara F, Muller U, Li Z, Lipp H, Weissmann C, Stagljar M, et al. Genetic background changes the pattern of forebrain commissure defects in transgenic mice underexpressing the beta-amyloid-precursor protein. Proc Natl Acad Sci U S A. 1999;96:4656-61 pubmed
    We previously have reported corpus callosum defects in transgenic mice expressing the beta-amyloid precursor protein (betaAPP) with a deletion of exon 2 and at only 5% of normal levels...
  5. Simakova O, Arispe N. The cell-selective neurotoxicity of the Alzheimer's Abeta peptide is determined by surface phosphatidylserine and cytosolic ATP levels. Membrane binding is required for Abeta toxicity. J Neurosci. 2007;27:13719-29 pubmed
    Measurement of Abeta toxicity of cells in culture exposes a subpopulation of cells with resistance to Abeta, even at high concentrations and after long periods of treatment...
  6. Liu Q, Zerbinatti C, Zhang J, HOE H, Wang B, Cole S, et al. Amyloid precursor protein regulates brain apolipoprotein E and cholesterol metabolism through lipoprotein receptor LRP1. Neuron. 2007;56:66-78 pubmed
    Mutations in the amyloid precursor protein (APP) cause early-onset Alzheimer's disease (AD), but the only genetic risk factor for late-onset AD is the varepsilon4 allele of apolipoprotein E (apoE), a major cholesterol carrier...
  7. Zerbinatti C, Wahrle S, Kim H, Cam J, Bales K, Paul S, et al. Apolipoprotein E and low density lipoprotein receptor-related protein facilitate intraneuronal Abeta42 accumulation in amyloid model mice. J Biol Chem. 2006;281:36180-6 pubmed
    ..protein (LRP) is highly expressed in the brain and has been shown to alter the metabolism of amyloid precursor protein and amyloid-beta peptide (Abeta) in vitro...
  8. McPhie D, Coopersmith R, Hines Peralta A, Chen Y, Ivins K, Manly S, et al. DNA synthesis and neuronal apoptosis caused by familial Alzheimer disease mutants of the amyloid precursor protein are mediated by the p21 activated kinase PAK3. J Neurosci. 2003;23:6914-27 pubmed
    ..We show that expression of familial AD (FAD) mutants of the amyloid precursor protein (APP) in primary neurons in culture causes apoptosis and DNA synthesis...
  9. Gimbel D, Nygaard H, Coffey E, Gunther E, Lauren J, Gimbel Z, et al. Memory impairment in transgenic Alzheimer mice requires cellular prion protein. J Neurosci. 2010;30:6367-74 pubmed publisher
    Soluble oligomers of the amyloid-beta (Abeta) peptide are thought to play a key role in the pathophysiology of Alzheimer's disease (AD)...

More Information

Publications82

  1. Jan A, Gokce O, Luthi Carter R, Lashuel H. The ratio of monomeric to aggregated forms of Abeta40 and Abeta42 is an important determinant of amyloid-beta aggregation, fibrillogenesis, and toxicity. J Biol Chem. 2008;283:28176-89 pubmed publisher
    Aggregation and fibril formation of amyloid-beta (Abeta) peptides Abeta40 and Abeta42 are central events in the pathogenesis of Alzheimer disease...
  2. Chong Y, Shin Y, Lee E, Kayed R, Glabe C, Tenner A. ERK1/2 activation mediates Abeta oligomer-induced neurotoxicity via caspase-3 activation and tau cleavage in rat organotypic hippocampal slice cultures. J Biol Chem. 2006;281:20315-25 pubmed
    ..investigated the molecular basis for the altered signal transduction associated with soluble amyloid beta-protein (Abeta) oligomer-mediated neurotoxicity in the hippocampus, which is primarily linked to cognitive dysfunction in ..
  3. Maloney B, Ge Y, Greig N, Lahiri D. Presence of a "CAGA box" in the APP gene unique to amyloid plaque-forming species and absent in all APLP-1/2 genes: implications in Alzheimer's disease. FASEB J. 2004;18:1288-90 pubmed publisher
    Potentially toxic amyloid beta-peptide (Abeta) in Alzheimer's disease (AD) is generated from a family of Abeta-containing precursor proteins (APP), which is regulated via the 5'-untranslated region (5'-UTR) of its mRNA...
  4. Dougherty J, Wu J, Nichols R. Beta-amyloid regulation of presynaptic nicotinic receptors in rat hippocampus and neocortex. J Neurosci. 2003;23:6740-7 pubmed
    Alteration by beta-amyloid (Abeta) of signaling via nicotinic acetylcholine receptors (nAChRs) has been implicated in the early stages of Alzheimer's disease...
  5. Zheng H, Jiang M, Trumbauer M, Sirinathsinghji D, Hopkins R, Smith D, et al. beta-Amyloid precursor protein-deficient mice show reactive gliosis and decreased locomotor activity. Cell. 1995;81:525-31 pubmed
    In several pedigrees of early onset familial Alzheimer's disease (FAD), point mutations in the beta-amyloid precursor protein (APP) gene are genetically linked to the disease...
  6. Muller U, Cristina N, Li Z, Wolfer D, Lipp H, Rülicke T, et al. Behavioral and anatomical deficits in mice homozygous for a modified beta-amyloid precursor protein gene. Cell. 1994;79:755-65 pubmed
    The beta-amyloid precursor protein (beta APP) gene of the mouse was disrupted by inserting into exon 2 a cassette containing a neomycin resistance gene and a putative transcription termination sequence...
  7. Huang X, Atwood C, Hartshorn M, Multhaup G, Goldstein L, Scarpa R, et al. The A beta peptide of Alzheimer's disease directly produces hydrogen peroxide through metal ion reduction. Biochemistry. 1999;38:7609-16 pubmed
    ..These findings indicate that the accumulation of A beta could be a direct source of oxidative stress in Alzheimer's disease. ..
  8. Borg J, Ooi J, Levy E, Margolis B. The phosphotyrosine interaction domains of X11 and FE65 bind to distinct sites on the YENPTY motif of amyloid precursor protein. Mol Cell Biol. 1996;16:6229-41 pubmed
    ..of X11 and one of the PI domains of FE65, two neuronal proteins, bind to the cytoplasmic domain of the amyloid precursor protein ((beta)APP). (beta)APP is an integral transmembrane glycoprotein whose cellular function is unknown...
  9. Goldsbury C, Mocanu M, Thies E, Kaether C, Haass C, Keller P, et al. Inhibition of APP trafficking by tau protein does not increase the generation of amyloid-beta peptides. Traffic. 2006;7:873-88 pubmed
    Amyloid-beta, a peptide derived from the precursor protein APP, accumulates in the brain and contributes to the neuropathology of Alzheimer's disease...
  10. Lazarov O, Morfini G, Lee E, Farah M, Szodorai A, DeBoer S, et al. Axonal transport, amyloid precursor protein, kinesin-1, and the processing apparatus: revisited. J Neurosci. 2005;25:2386-95 pubmed
    ..enzyme 1 (BACE1), presenilins (PS), and other proteins of the gamma-secretase complex liberate beta-amyloid (Abeta) peptides from larger integral membrane proteins, termed beta-amyloid precursor proteins (APPs)...
  11. Watanabe T, Sukegawa J, Sukegawa I, Tomita S, Iijima K, Oguchi S, et al. A 127-kDa protein (UV-DDB) binds to the cytoplasmic domain of the Alzheimer's amyloid precursor protein. J Neurochem. 1999;72:549-56 pubmed
    Alzheimer amyloid precursor protein (APP) is an integral membrane protein with a short cytoplasmic domain of 47 amino acids...
  12. Soba P, Eggert S, Wagner K, Zentgraf H, Siehl K, Kreger S, et al. Homo- and heterodimerization of APP family members promotes intercellular adhesion. EMBO J. 2005;24:3624-34 pubmed
    The amyloid precursor protein (APP) plays a central role in Alzheimer's disease, but its physiological function and that of its mammalian paralogs, the amyloid precursor-like proteins 1 and 2 (APLPs), is still poorly understood...
  13. Ladiwala A, Lin J, Bale S, Marcelino Cruz A, Bhattacharya M, Dordick J, et al. Resveratrol selectively remodels soluble oligomers and fibrils of amyloid Abeta into off-pathway conformers. J Biol Chem. 2010;285:24228-37 pubmed publisher
    ..Surprisingly, resveratrol does not remodel non-toxic oligomers or accelerate Abeta monomer aggregation despite that both conformers possess random coil secondary structures indistinguishable from ..
  14. Pardossi Piquard R, Petit A, Kawarai T, Sunyach C, Alves da Costa C, Vincent B, et al. Presenilin-dependent transcriptional control of the Abeta-degrading enzyme neprilysin by intracellular domains of betaAPP and APLP. Neuron. 2005;46:541-54 pubmed
    ..role in Alzheimer's disease, is generated by presenilin-dependent gamma-secretase cleavage of beta-amyloid precursor protein (betaAPP). We report that the presenilins (PS1 and PS2) also regulate Abeta degradation...
  15. Herms J, Anliker B, Heber S, Ring S, Fuhrmann M, Kretzschmar H, et al. Cortical dysplasia resembling human type 2 lissencephaly in mice lacking all three APP family members. EMBO J. 2004;23:4106-15 pubmed
    The Alzheimer's disease beta-amyloid precursor protein (APP) is a member of a larger gene family that includes the amyloid precursor-like proteins, termed APLP1 and APLP2...
  16. Hiruma H, Katakura T, Takahashi S, Ichikawa T, Kawakami T. Glutamate and amyloid beta-protein rapidly inhibit fast axonal transport in cultured rat hippocampal neurons by different mechanisms. J Neurosci. 2003;23:8967-77 pubmed
    Impairment of axonal transport leads to neurodegeneration and synapse loss. Glutamate and amyloid beta-protein (Abeta) have critical roles in the pathogenesis of Alzheimer's disease (AD)...
  17. Vagnoni A, Perkinton M, Gray E, Francis P, Noble W, Miller C. Calsyntenin-1 mediates axonal transport of the amyloid precursor protein and regulates A? production. Hum Mol Genet. 2012;21:2845-54 pubmed publisher
    Understanding the mechanisms that control processing of the amyloid precursor protein (APP) to produce amyloid-? (A?) peptide represents a key area of Alzheimer's disease research...
  18. Säljö A, Bao F, Shi J, Hamberger A, Hansson H, Haglid K. Expression of c-Fos and c-Myc and deposition of beta-APP in neurons in the adult rat brain as a result of exposure to short-lasting impulse noise. J Neurotrauma. 2002;19:379-85 pubmed
    ..Here, rat brains were investigated immunohistochemically for the expression of c-Fos, c-Myc, and beta-APP during the first 3 weeks postexposure to impulse noise of 198 or 202 dB...
  19. Vitolo O, Sant Angelo A, Costanzo V, Battaglia F, Arancio O, Shelanski M. Amyloid beta -peptide inhibition of the PKA/CREB pathway and long-term potentiation: reversibility by drugs that enhance cAMP signaling. Proc Natl Acad Sci U S A. 2002;99:13217-21 pubmed
    ..In the studies reported here we demonstrate that amyloid beta-peptide (Abeta) treatment of cultured hippocampal neurons leads to the inactivation of protein kinase A (PKA) and persistence of ..
  20. Abramov E, Dolev I, Fogel H, Ciccotosto G, Ruff E, Slutsky I. Amyloid-beta as a positive endogenous regulator of release probability at hippocampal synapses. Nat Neurosci. 2009;12:1567-76 pubmed publisher
    Accumulation of cerebral amyloid-beta peptide (Abeta) is essential for developing synaptic and cognitive deficits in Alzheimer's disease...
  21. Madeira A, Pommet J, Prochiantz A, Allinquant B. SET protein (TAF1beta, I2PP2A) is involved in neuronal apoptosis induced by an amyloid precursor protein cytoplasmic subdomain. FASEB J. 2005;19:1905-7 pubmed
    When overexpressed, a short cytoplasmic domain of the amyloid precursor protein (APP), normally unmasked in the brain of Alzheimer's disease patients, activates caspase-3 and induces neuronal death...
  22. Sabo S, Ikin A, Buxbaum J, Greengard P. The amyloid precursor protein and its regulatory protein, FE65, in growth cones and synapses in vitro and in vivo. J Neurosci. 2003;23:5407-15 pubmed
    Although the Alzheimer amyloid protein precursor (APP) has been studied intensely for more than a decade, its function in neurons is unresolved. Much less is known about its binding partner FE65...
  23. HOE H, Lee K, Carney R, Lee J, Markova A, Lee J, et al. Interaction of reelin with amyloid precursor protein promotes neurite outgrowth. J Neurosci. 2009;29:7459-73 pubmed publisher
    The processing of amyloid precursor protein (APP) to Abeta is an important event in the pathogenesis of Alzheimer's disease, but the physiological function of APP is not well understood...
  24. Alarcón R, Fuenzalida C, Santibañez M, von Bernhardi R. Expression of scavenger receptors in glial cells. Comparing the adhesion of astrocytes and microglia from neonatal rats to surface-bound beta-amyloid. J Biol Chem. 2005;280:30406-15 pubmed
    ..Microglia are activated by and can phagocytose beta-amyloid (Abeta). Scavenger receptors (SRs) are among the receptors mediating the uptake of fibrillar Abeta in vitro...
  25. Jin L, Ninomiya H, Roch J, Schubert D, Masliah E, Otero D, et al. Peptides containing the RERMS sequence of amyloid beta/A4 protein precursor bind cell surface and promote neurite extension. J Neurosci. 1994;14:5461-70 pubmed
    Amyloid beta/A4 protein precursor (APP) is secreted into medium by most cultured cells and can function as an autocrine factor...
  26. von Koch C, Zheng H, Chen H, Trumbauer M, Thinakaran G, Van der Ploeg L, et al. Generation of APLP2 KO mice and early postnatal lethality in APLP2/APP double KO mice. Neurobiol Aging. 1997;18:661-9 pubmed
    b>Amyloid precursor protein (APP) is a member of a larger gene family including amyloid precursor-like proteins (APLP), APLP2 and APLP1. To examine the function of APLP2 in vivo, we generated APLP2 knockout (KO) mice...
  27. Vetrivel K, Cheng H, Kim S, Chen Y, Barnes N, Parent A, et al. Spatial segregation of gamma-secretase and substrates in distinct membrane domains. J Biol Chem. 2005;280:25892-900 pubmed
    ..In this study, we used biochemical approaches to examine the distribution of amyloid precursor protein (APP) and several additional gamma-secretase substrates in membrane microdomains...
  28. Kim J, Hamamoto S, Ravazzola M, Orci L, Schekman R. Uncoupled packaging of amyloid precursor protein and presenilin 1 into coat protein complex II vesicles. J Biol Chem. 2005;280:7758-68 pubmed
    Mutant forms of presenilin (PS) 1 and 2 and amyloid precursor protein (APP) lead to familial Alzheimer's disease. Several reports indicate that PS may modulate APP export from the endoplasmic reticulum (ER)...
  29. Basha M, Wei W, Bakheet S, Benitez N, Siddiqi H, Ge Y, et al. The fetal basis of amyloidogenesis: exposure to lead and latent overexpression of amyloid precursor protein and beta-amyloid in the aging brain. J Neurosci. 2005;25:823-9 pubmed
    ..by excessive deposits of aggregated beta-amyloid (Abeta) peptides, which are snippets of the beta-amyloid precursor protein (APP)...
  30. Shankar G, Li S, Mehta T, Garcia Munoz A, Shepardson N, Smith I, et al. Amyloid-beta protein dimers isolated directly from Alzheimer's brains impair synaptic plasticity and memory. Nat Med. 2008;14:837-42 pubmed publisher
    ..We extracted soluble amyloid-beta protein (Abeta) oligomers directly from the cerebral cortex of subjects with Alzheimer's disease...
  31. Sannerud R, Declerck I, Peric A, Raemaekers T, Menendez G, Zhou L, et al. ADP ribosylation factor 6 (ARF6) controls amyloid precursor protein (APP) processing by mediating the endosomal sorting of BACE1. Proc Natl Acad Sci U S A. 2011;108:E559-68 pubmed publisher
    ..and a hallmark in Alzheimer's disease pathology, are generated through the sequential cleavage of amyloid precursor protein (APP) by ?-site APP cleaving enzyme 1 (BACE1) and ?-secretase...
  32. Westerman M, Cooper Blacketer D, Mariash A, Kotilinek L, Kawarabayashi T, Younkin L, et al. The relationship between Abeta and memory in the Tg2576 mouse model of Alzheimer's disease. J Neurosci. 2002;22:1858-67 pubmed
    ..APP (Tg2576 mice) starting at approximately 6 months, which coincided with the appearance of detergent-insoluble Abeta aggregates (Abeta(insol))...
  33. Zhu D, Shi J, Zhang Y, Wang B, Liu W, Chen Z, et al. Central angiotensin II stimulation promotes ? amyloid production in Sprague Dawley rats. PLoS ONE. 2011;6:e16037 pubmed publisher
    ..Ang II infusion, the stimulation of Ang II type 1 receptors was accompanied by the modulation of amyloid precursor protein, ?-, ?-and ?-secretase, and increased ? amyloid production...
  34. Dawson G, Seabrook G, Zheng H, Smith D, Graham S, O Dowd G, et al. Age-related cognitive deficits, impaired long-term potentiation and reduction in synaptic marker density in mice lacking the beta-amyloid precursor protein. Neuroscience. 1999;90:1-13 pubmed
    Mutations in the beta-amyloid precursor protein are strongly associated with some cases of familial Alzheimer's disease...
  35. Sarell C, Wilkinson S, Viles J. Substoichiometric levels of Cu2+ ions accelerate the kinetics of fiber formation and promote cell toxicity of amyloid-{beta} from Alzheimer disease. J Biol Chem. 2010;285:41533-40 pubmed publisher
    ..An active role for Cu(2+) ions in accelerating fiber formation and promoting cell death suggests impaired copper homeostasis may be a risk factor in Alzheimer disease. ..
  36. Cisse M, Halabisky B, Harris J, Devidze N, Dubal D, Sun B, et al. Reversing EphB2 depletion rescues cognitive functions in Alzheimer model. Nature. 2011;469:47-52 pubmed publisher
    ..Increasing EphB2 expression in the dentate gyrus of human amyloid precursor protein transgenic mice reversed deficits in NMDA receptor-dependent long-term potentiation and memory ..
  37. Olah J, Vincze O, Virok D, Simon D, Bozso Z, Tökési N, et al. Interactions of pathological hallmark proteins: tubulin polymerization promoting protein/p25, beta-amyloid, and alpha-synuclein. J Biol Chem. 2011;286:34088-100 pubmed publisher
  38. Nadezhdin K, Bocharova O, Bocharov E, Arseniev A. Dimeric structure of transmembrane domain of amyloid precursor protein in micellar environment. FEBS Lett. 2012;586:1687-92 pubmed publisher
    ..Alzheimer's disease are thought to affect structural-dynamic properties and the lateral dimerization of amyloid precursor protein (APP) in neuron membrane...
  39. Horiuchi M, Maezawa I, Itoh A, Wakayama K, Jin L, Itoh T, et al. Amyloid ?1-42 oligomer inhibits myelin sheet formation in vitro. Neurobiol Aging. 2012;33:499-509 pubmed publisher
  40. Qiu Y, Wu X, Chen H. Simultaneous changes in secretory amyloid precursor protein and beta-amyloid peptide release from rat hippocampus by activation of muscarinic receptors. Neurosci Lett. 2003;352:41-4 pubmed
    ..Alzheimer's disease (AD) are composed of beta-amyloid peptides (Abeta) that are derived from the larger amyloid precursor protein (APP)...
  41. Yamazaki T, Yamaguchi H, Kawarabayashi T, Hirai S. Ultrastructural localization of amyloid beta/A4 protein precursor in the normal rat brain. Virchows Arch B Cell Pathol Incl Mol Pathol. 1993;63:173-80 pubmed
    The ultrastructural localization of amyloid beta/A4 protein precursor (APP) was studied immunohistochemically in normal rat brains using antibodies against different portions of APP. In cerebral cortical neurons and Purkinje cells...
  42. Marquez Sterling N, Lo A, Sisodia S, Koo E. Trafficking of cell-surface beta-amyloid precursor protein: evidence that a sorting intermediate participates in synaptic vesicle recycling. J Neurosci. 1997;17:140-51 pubmed
    We recently demonstrated that the Alzheimer's beta-amyloid precursor protein (APP) is internalized from the axonal cell surface...
  43. Wu M, He Y, Guo F, Qi J. Alpha4beta2 nicotinic acetylcholine receptors are required for the amyloid beta protein-induced suppression of long-term potentiation in rat hippocampal CA1 region in vivo. Brain Res Bull. 2008;77:84-90 pubmed publisher
    Amyloid beta protein (Abeta) is thought to be responsible for the deficit of learning and memory in Alzheimer's disease (AD), possibly through interfering with synaptic plasticity such as hippocampal long-term potentiation (LTP)...
  44. Dziewczapolski G, Glogowski C, Masliah E, Heinemann S. Deletion of the alpha 7 nicotinic acetylcholine receptor gene improves cognitive deficits and synaptic pathology in a mouse model of Alzheimer's disease. J Neurosci. 2009;29:8805-15 pubmed publisher
    ..in AD pathogenesis, we used a transgenic mouse model of AD overexpressing a mutated form of the human amyloid precursor protein (APP) and lacking the alpha7nAChR gene (APPalpha7KO)...
  45. Shankar G, Leissring M, Adame A, Sun X, Spooner E, Masliah E, et al. Biochemical and immunohistochemical analysis of an Alzheimer's disease mouse model reveals the presence of multiple cerebral Abeta assembly forms throughout life. Neurobiol Dis. 2009;36:293-302 pubmed publisher
    The amyloid beta-protein (Abeta) is believed to play a causal role in Alzheimer's disease, however, the mechanism by which Abeta mediates its effect and the assembly form(s) of Abeta responsible remain unclear...
  46. Wei W, Nguyen L, Kessels H, Hagiwara H, Sisodia S, Malinow R. Amyloid beta from axons and dendrites reduces local spine number and plasticity. Nat Neurosci. 2010;13:190-6 pubmed publisher
    Excessive synaptic loss is thought to be one of the earliest events in Alzheimer's disease. Amyloid beta (Abeta), a peptide secreted in an activity-modulated manner by neurons, has been implicated in the pathogenesis of Alzheimer's ..
  47. Frånberg J, Karlstrom H, Winblad B, Tjernberg L, Frykman S. gamma-Secretase dependent production of intracellular domains is reduced in adult compared to embryonic rat brain membranes. PLoS ONE. 2010;5:e9772 pubmed publisher
    gamma-Secretase is an intramembrane aspartyl protease whose cleavage of the amyloid precursor protein (APP) generates the amyloid beta-peptide (Abeta) and the APP intracellular domain...
  48. Duilio A, Faraonio R, Minopoli G, Zambrano N, Russo T. Fe65L2: a new member of the Fe65 protein family interacting with the intracellular domain of the Alzheimer's beta-amyloid precursor protein. Biochem J. 1998;330 ( Pt 1):513-9 pubmed
    We previously demonstrated that Fe65 protein is one of the ligands of the cytoplasmic domain of beta-amyloid precursor protein (APP)...
  49. Zhao W, Lacor P, Chen H, Lambert M, Quon M, Krafft G, et al. Insulin receptor dysfunction impairs cellular clearance of neurotoxic oligomeric a{beta}. J Biol Chem. 2009;284:18742-53 pubmed publisher
    Accumulation of amyloid beta (Abeta) oligomers in the brain is toxic to synapses and may play an important role in memory loss in Alzheimer disease. However, how these toxins are built up in the brain is not understood...
  50. Pasternak S, Bagshaw R, Guiral M, Zhang S, Ackerley C, Pak B, et al. Presenilin-1, nicastrin, amyloid precursor protein, and gamma-secretase activity are co-localized in the lysosomal membrane. J Biol Chem. 2003;278:26687-94 pubmed
    ..deposition of beta-amyloid (Abeta), a 38-43-amino acid peptide derived by proteolytic cleavage of the amyloid precursor protein (APP)...
  51. Chen X, Yang Y, Zhang Y. Isobavachalcone and bavachinin from Psoraleae Fructus modulate A?42 aggregation process through different mechanisms in vitro. FEBS Lett. 2013;587:2930-5 pubmed publisher
    ..Both of the compounds attenuated A?42-induced toxicity in a SH-SY5Y cell model. These findings may provide valuable information for new drug development and Alzheimer's therapy in the future. ..
  52. Lei Y, Yang L, Ye C, Qin M, Yang H, Jiang H, et al. Involvement of Intracellular and Mitochondrial Aβ in the Ameliorative Effects of Huperzine A against Oligomeric Aβ42-Induced Injury in Primary Rat Neurons. PLoS ONE. 2015;10:e0128366 pubmed publisher
    ..Above results may shed more light on the pharmacological mechanisms of huperzine A and provide important clues for discovering novel therapeutic strategies for AD. ..
  53. Park S, Jung H, Kim Y, Park T, Kim C, Choi H, et al. Asp664 cleavage of amyloid precursor protein induces tau phosphorylation by decreasing protein phosphatase 2A activity. J Neurochem. 2012;123:856-65 pubmed publisher
    Caspase cleavage of amyloid precursor protein (APP) has been reported to be important in amyloid beta protein (A?)-mediated neurotoxicity. However, the underlying mechanisms are not clearly understood...
  54. Nakagawa T, Kabuto M, Kubota T, Kodera T, Sato K. Production of amyloid beta protein precursor as a proteinase inhibitor by human astrocytic tumors. Anticancer Res. 1999;19:2963-8 pubmed
    The production of amyloid beta protein precursor (APP), which is a potent inhibitor of matrix metalloproteinases and serine proteinases, in human astrocytic tumors (n = 17) and normal brain tissues (n = 3) was investigated...
  55. Xu W, Weissmiller A, White J, Fang F, Wang X, Wu Y, et al. Amyloid precursor protein-mediated endocytic pathway disruption induces axonal dysfunction and neurodegeneration. J Clin Invest. 2016;126:1815-33 pubmed publisher
    ..We determined that full-length amyloid precursor protein (APP) and its ?-C-terminal fragment (?-CTF) act though increased activation of Rab5 to cause enlargement ..
  56. White A, Reyes R, Mercer J, Camakaris J, Zheng H, Bush A, et al. Copper levels are increased in the cerebral cortex and liver of APP and APLP2 knockout mice. Brain Res. 1999;842:439-44 pubmed
    ..The neurotoxic Abeta peptide is derived from the amyloid precursor protein (APP), a member of a larger gene family including the amyloid precursor-like proteins, APLP1 and APLP2...
  57. Sanchez Alavez M, Chan S, Mattson M, Criado J. Electrophysiological and cerebrovascular effects of the alpha-secretase-derived form of amyloid precursor protein in young and middle-aged rats. Brain Res. 2007;1131:112-7 pubmed
    Cleavage of the beta-amyloid precursor protein (APP) by alpha-secretase releases a secreted form of APP (sAPP) from cells...
  58. Kirouac L, Rajic A, Cribbs D, Padmanabhan J. Activation of Ras-ERK Signaling and GSK-3 by Amyloid Precursor Protein and Amyloid Beta Facilitates Neurodegeneration in Alzheimer's Disease. Eneuro. 2017;4: pubmed publisher
    It is widely accepted that amyloid ? (A?) generated from amyloid precursor protein (APP) oligomerizes and fibrillizes to form neuritic plaques in Alzheimer's disease (AD), yet little is known about the contribution of APP to ..
  59. Tran M. P2 receptor stimulation induces amyloid precursor protein production and secretion in rat cortical astrocytes. Neurosci Lett. 2011;492:155-9 pubmed publisher
    b>Amyloid precursor protein (APP) is ubiquitously expressed in a variety of tissues but is predominantly expressed in the brain. The expression of APP has been well studied in neurons but little is known about its presence in astrocytes...
  60. Shen L, Ji H. Rat's trick to escape Alzheimer's disease. J Biomol Struct Dyn. 2007;25:271-4 pubmed
    Amyloid beta (Abeta) peptides fibril formation and deposition is considered to be the principal pathological hallmark of Alzheimer's disease (AD)...
  61. Kogel D, Schomburg R, Schürmann T, Reimertz C, König H, Poppe M, et al. The amyloid precursor protein protects PC12 cells against endoplasmic reticulum stress-induced apoptosis. J Neurochem. 2003;87:248-56 pubmed
    ..In the present study, we investigated the effect of the human amyloid precursor protein (APP) on the ER stress response in PC12 cells...
  62. Moreth J, Kroker K, Schwanzar D, Schnack C, von Arnim C, Hengerer B, et al. Globular and protofibrillar a? aggregates impair neurotransmission by different mechanisms. Biochemistry. 2013;52:1466-76 pubmed publisher
    ..Thus, we emphasize the importance of addressing the metastability of prefacto characterized A? aggregates in assigning a biological effect. ..
  63. Seixas da Silva G, Melo H, Lourenco M, Lyra e Silva N, de Carvalho M, Alves Leon S, et al. Amyloid-β oligomers transiently inhibit AMP-activated kinase and cause metabolic defects in hippocampal neurons. J Biol Chem. 2017;292:7395-7406 pubmed publisher
    ..Our results establish a novel toxic impact of AβOs on neuronal metabolism and suggest that AβO-induced, NMDA receptor-mediated AMPK inhibition may play a key role in early brain metabolic defects in AD. ..
  64. Misawa T, Arima K, Mizusawa H, Satoh J. Close association of water channel AQP1 with amyloid-beta deposition in Alzheimer disease brains. Acta Neuropathol. 2008;116:247-60 pubmed publisher
    ..By immunoprecipitation, the C-terminal fragment-beta (CTFbeta) of amyloid precursor protein interacted with the N-terminal half of AQP1 spanning the transmembrane helices H1, H2 and H3...
  65. Jin Y, Tsuchiya A, Kanno T, Nishizaki T. Amyloid-β peptide increases cell surface localization of α7 ACh receptor to protect neurons from amyloid β-induced damage. Biochem Biophys Res Commun. 2015;468:157-60 pubmed publisher
    ..Taken together, these results indicate that Aβ1-42 promotes translocation of α7 ACh receptor towards the cell surface and that α7 ACh receptor rescues neuronal cells from Aβ1-42-induced damage. ..
  66. Lee R, Araki W, Wurtman R. Stimulation of amyloid precursor protein synthesis by adrenergic receptors coupled to cAMP formation. Proc Natl Acad Sci U S A. 1997;94:5422-6 pubmed
    Amyloid plaques in Alzheimer disease are primarily aggregates of Abeta peptides that are derived from the amyloid precursor protein (APP)...
  67. López Sánchez N, Muller U, Frade J. Lengthening of G2/mitosis in cortical precursors from mice lacking beta-amyloid precursor protein. Neuroscience. 2005;130:51-60 pubmed
    The beta-amyloid precursor protein (APP) is expressed within the nervous system, even at the earliest stages of embryonic development when cell growth and proliferation is particularly important...
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