The many faces of autophagy dysfunction in Huntington's disease: from mechanism to therapy.
The many faces of autophagy dysfunction in Huntington's disease: from mechanism to therapy.
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DOI：
10.1016/j.drudis.2014.02.014
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发表时间：
2014-07
影响因子：
7.4
通讯作者：
La Spada, Albert R.
中科院分区：
文献类型：
--
作者：
Cortes, Constanza J.;La Spada, Albert R.
自噬是蛋白质、大分子和细胞器靶向溶酶体并被溶酶体降解的细胞过程。鉴于神经退行性疾病涉及产生无法被细胞蛋白质质量控制系统降解的错误折叠蛋白质，自噬途径现在成为密切关注的焦点，因为自噬主要负责维持中枢神经系统（CNS）中正常的细胞蛋白质稳态。亨廷顿病 (HD) 是一种遗传性 CAG-聚谷氨酰胺重复序列紊乱，由错误折叠亨廷顿 (Htt) 蛋白的产生和积累引起。 HD 与阿尔茨海默病 (AD) 和帕金森病 (PD) 等常见神经退行性疾病具有相同的关键特征，因此属于一大类称为神经退行性蛋白病的疾病。多项独立研究已经记录了 HD 中自噬功能的改变，并且大量研究已经证明自噬调节作为治疗干预的潜在作用。在这篇综述中，我们考虑了 HD 中自噬功能障碍的证据，并描述了可能解释 HD 中检测到的自噬异常的不同靶点和机制途径。我们评估了自噬调节作为 HD 治疗方式的效用，并针对 HD 及相关疾病的自噬途径的未来治疗开发提出了指南和注意事项。
Autophagy is the cellular process by which proteins, macromolecules, and organelles are targeted to and degraded by the lysosome. Given that neurodegenerative diseases involve the production of misfolded proteins that cannot be degraded by the protein quality-control systems of the cell, the autophagy pathway is now the focus of intense scrutiny, because autophagy is primarily responsible for maintaining normal cellular proteostasis in the central nervous system (CNS). Huntington's disease (HD) is an inherited CAG–polyglutamine repeat disorder, resulting from the production and accumulation of misfoldedhuntingtin (Htt) protein. HD shares key features with common neurodegenerative disorders, such as Alzheimer's disease (AD) and Parkinson's disease (PD) and, thus, belongs to a large class of disorders known as neurodegenerative proteinopathies. Multiple independent lines of research have documented alterations in autophagy function in HD, and numerous studies have demonstrated a potential role for autophagy modulation as a therapeutic intervention. In this review, we consider the evidence for autophagy dysfunction in HD, and delineate different targets and mechanistic pathways that might account for the autophagy abnormalities detected in HD. We assess the utility of autophagy modulation as a treatment modality in HD, and suggest guidelines and caveats for future therapy development directed at the autophagy pathway in HD and related disorders.
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DOI：
10.1083/jcb.201110093
发表时间：
2012-03-05
期刊：
The Journal of cell biology
影响因子：
--
作者：
Hipp MS;Patel CN;Bersuker K;Riley BE;Kaiser SE;Shaler TA;Brandeis M;Kopito RR
通讯作者：
Kopito RR
影响因子：
4.2
作者：
Garcia-Martinez, Juan M.;Perez-Navarro, Esther;Albech, Jordi
通讯作者：
Albech, Jordi
影响因子：
10.5
作者：
Duennwald, Martin L.;Lindquist, Susan
通讯作者：
Lindquist, Susan
影响因子：
13.3
作者：
Atwal, Randy Singh;Truant, Ray
通讯作者：
Truant, Ray
影响因子：
4.8
作者：
Carnemolla, Alisia;Fossale, Elisa;Persichetti, Francesca
通讯作者：
Persichetti, Francesca