title: APP processing in Alzheimer's disease.
abstract: An important pathological feature of Alzheimer's disease (AD) is the presence of extracellular senile plaques in the brain. Senile plaques are composed of aggregations of small peptides called β-amyloid (Aβ). Multiple lines of evidence demonstrate that overproduction/aggregation of Aβ in the brain is a primary cause of AD and inhibition of Aβ generation has become a hot topic in AD research. Aβ is generated from β-amyloid precursor protein (APP) through sequential cleavages first by β-secretase and then by γ-secretase complex. Alternatively, APP can be cleaved by α-secretase within the Aβ domain to release soluble APPα and preclude Aβ generation. Cleavage of APP by caspases may also contribute to AD pathologies. Therefore, understanding the metabolism/processing of APP is crucial for AD therapeutics. Here we review current knowledge of APP processing regulation as well as the patho/physiological functions of APP and its metabolites.
authors.affiliation: Institute for Biomedical Research, Xiamen University, 422 SiMingNanLu, Xiamen 361005, Fujian, PR China.
authors.forename: Yun-wu
authors.initials: YW
authors.lastname: Zhang
authors.forename: Robert
authors.initials: R
authors.lastname: Thompson
authors.forename: Han
authors.initials: H
authors.lastname: Zhang
authors.forename: Huaxi
authors.initials: H
authors.lastname: Xu
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000096:biosynthesis / Q000235:genetics; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D020169:Caspases / Q000378:metabolism; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D058225:Plaque, Amyloid / Q000473:pathology; D015398:Signal Transduction / Q000502:physiology
chemical_list: C545487:APP protein, human; D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D007527:Isoenzymes; D053829:Amyloid Precursor Protein Secretases; D020169:Caspases