title: Relationship between amyloid-beta and the ubiquitin-proteasome system in Alzheimer's disease.
abstract: Amyloid-beta (Abeta) peptide is the original causative factor of Alzheimer's disease (AD) according to the amyloid cascade hypothesis. The ubiquitin-proteasome system (UPS), the major intracellular protein quality control system in eukaryotic cells, is related to AD pathogenesis. There is growing evidence showing that there is a tight relationship between Abeta and UPS and this relationship plays an important role in AD pathogenesis. This article reviews the relationship between Abeta and the UPS in terms of the following three aspects: the interaction of the two factors, the ubiquitinating process of Abeta, and impact of dysfunctional UPS on Abeta production. The impairment in the UPS in AD could affect the degradation of Abeta and lead to an abnormal accumulation of Abeta. At the same time, Abeta inhibits the proteasomal activity and subsequently leads to impairment of multivesicular bodies (MVB) sorting pathway, forming an interacting relationship between Abeta and UPS. Mutant ubiquitin (Ub) and ubiquitin-like (UBL) ubiquilin-1 are related to Abeta accumulation. Meanwhile E2 conjugating enzymes, E3 ligases, and de-ubiquitinating enzymes, all of which function in the ubiquitination process, play a pivotal role in the proteasomal degradation of Abeta. Ubiquitin-proteasome system has an immense impact on the amyloidogenic pathway of amyloid precursor protein (APP) processing that generates Abeta. Upregulation in proteasomal degradation of BACE1 and components of gamma-secretase leads to decreased Abeta accumulation. A deep look into the mechanism underlying the interplay between Abeta and UPS may provide alternative therapeutic targets and lead to new drugs and therapies.
authors: Liang
authors: L
authors: Hong
authors: Han-Chang
authors: HC
authors: Huang
authors: Zhao-Feng
authors: ZF
authors: Jiang
mesh_terms: D000544:Alzheimer Disease / Q000201:enzymology* / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D006801:Humans; D051379:Mice; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D025801:Ubiquitin / Q000378:metabolism*; D054875:Ubiquitination
chemical_list: D016229:Amyloid beta-Peptides; D025801:Ubiquitin; D046988:Proteasome Endopeptidase Complex
keywords: Alzheimer’s disease,; Amyloid-beta,; Degradation,; Proteasome,; Ubiquitin