The emerging roles of protein homeostasis-governing pathways in Alzheimer's disease.
The emerging roles of protein homeostasis-governing pathways in Alzheimer's disease.
复制标题
蛋白质稳态调控通路在阿尔茨海默病中的新作用。
作者：
Cheng J;North BJ;Zhang T;Dai X;Tao K;Guo J;Wei W
控制蛋白质稳态的途径涉及维持细胞内蛋白质的结构、数量和功能稳定性，并涉及遍在蛋白-蛋白酶体系统、自噬、内质网和mTOR途径。由于蛋白质稳态途径的广泛生理学意义，蛋白质稳态的失调通常涉及多种病理状况的发展，包括阿尔茨海默病（AD）。与其他以错误折叠蛋白质的致病性积累为特征的神经退行性疾病相似，阿尔茨海默病的特征在于两个病理学标志，淀粉样蛋白-β（Aβ）斑块和tau聚集体。小鼠中各种蛋白质抑制组分的敲除或转基因过表达导致AD样表型。而Aβ斑块和tau蛋白聚集体反过来又可以增强这些蛋白质抑制途径的功能障碍，最终导致神经元凋亡或坏死性死亡和阿尔茨海默病的发病机制。因此，靶向蛋白质代谢抑制通路的组分可能是对抗阿尔茨海默病的有希望的治疗策略。
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.
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影响因子：
168.9
作者：
Ballard, Clive;Gauthier, Serge;Jones, Emma
通讯作者：
Jones, Emma
YKL-40：一种用于临床前阿尔茨海默病的新型预后液体生物标志物。
影响因子：
10.6
作者：
Craig-Schapiro, Rebecca;Perrin, Richard J.;Roe, Catherine M.;Xiong, Chengjie;Carter, Deborah;Cairns, Nigel J.;Mintun, Mark A.;Peskind, Elaine R.;Li, Ge;Galasko, Douglas R.;Clark, Christopher M.;Quinn, Joseph F.;D'Angelo, Gina;Malone, James P.;Townsend, R. Reid;Morris, John C.;Fagan, Anne M.;Holtzman, David M.
通讯作者：
Holtzman, David M.
DOI：
10.1038/nri.2016.100
发表时间：
2016-11
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
Cadwell K
通讯作者：
Cadwell K
影响因子：
4.3
作者：
Calderwood SK;Murshid A
通讯作者：
Murshid A
影响因子：
3.2
作者：
Cai Z;Chen G;He W;Xiao M;Yan LJ
通讯作者：
Yan LJ