Open AccessThe emerging roles of protein homeostasis‐governing pathways in Alzheimer's disease
Author(s) -
Cheng Ji,
North Brian J.,
Zhang Tao,
Dai Xiangpeng,
Tao Kaixiong,
Guo Jianping,
Wei Wenyi
Publication year - 2018
Publication title -
aging cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.103
H-Index - 140
eISSN - 1474-9726
pISSN - 1474-9718
DOI - 10.1111/acel.12801
Subject(s) - proteostasis , biology , autophagy , unfolded protein response , neurodegeneration , proteasome , microbiology and biotechnology , protein aggregation , endoplasmic reticulum , homeostasis , disease , apoptosis , genetics , medicine , pathology
Pathways governing protein homeostasis are involved in maintaining the structural, quantitative, and functional stability of intracellular proteins and involve the ubiquitin–proteasome system, autophagy, endoplasmic reticulum, and mTOR pathway. Due to the broad physiological implications of protein homeostasis pathways, dysregulation of proteostasis is often involved in the development of multiple pathological conditions, including Alzheimer's disease ( AD ). Similar to other neurodegenerative diseases that feature pathogenic accumulation of misfolded proteins, Alzheimer's disease is characterized by two pathological hallmarks, amyloid‐β (Aβ) plaques and tau aggregates. Knockout or transgenic overexpression of various proteostatic components in mice results in AD ‐like phenotypes. While both Aβ plaques and tau aggregates could in turn enhance the dysfunction of these proteostatic pathways, eventually leading to apoptotic or necrotic neuronal death and pathogenesis of Alzheimer's disease. Therefore, targeting the components of proteostasis pathways may be a promising therapeutic strategy against Alzheimer's disease.