Autophagy and polyglutamine diseases.
Autophagy and polyglutamine diseases.
复制标题
DOI：
10.1016/j.pneurobio.2011.08.013
复制
发表时间：
2012-05
影响因子：
6.7
通讯作者：
Rubinsztein, David C.
中科院分区：
文献类型：
--
作者：
Jimenez-Sanchez, Maria;Thomson, Frances;Zavodszky, Eszter;Rubinsztein, David C.
泛素-蛋白酶体系统和自噬是两种主要的降解途径。自噬上调可防止聚谷氨酰胺扩展蛋白的神经毒性。某些神经退行性疾病可能发生自噬损害。在聚谷氨酰胺疾病中，异常延长的聚谷氨酰胺束导致蛋白质错误折叠和细胞内聚集体的积累。聚谷氨酰胺扩增的长度与突变蛋白聚集的倾向有关，也与神经元毒性和早期发病有关。虽然目前还没有有效的治疗方法来预防或减缓这些神经退行性疾病的进展，但增加突变蛋白的清除已被提出作为一种潜在的治疗方法。泛素-蛋白酶体系统和自噬是两种主要的降解途径，负责消除细胞中错误折叠和不必要的蛋白质。我们将回顾一些提出自噬作为减少聚谷氨酰胺扩增蛋白聚集体积累和防止突变蛋白神经毒性的策略的研究。我们还将讨论一些目前已知的诱导自噬的机制，这可能对这些和其他神经退行性疾病的治疗有益。
► The ubiquitin–proteasome system and autophagy are two main degradative pathways. ► Autophagy upregulation may protect against polyglutamine-expanded protein neurotoxicity. ► Autophagy compromise may occur in certain neurodegenerative diseases. In polyglutamine diseases, an abnormally elongated polyglutamine tract results in protein misfolding and accumulation of intracellular aggregates. The length of the polyglutamine expansion correlates with the tendency of the mutant protein to aggregate, as well as with neuronal toxicity and earlier disease onset. Although currently there is no effective cure to prevent or slow down the progression of these neurodegenerative disorders, increasing the clearance of mutant proteins has been proposed as a potential therapeutic approach. The ubiquitin–proteasome system and autophagy are the two main degradative pathways responsible for eliminating misfolded and unnecessary proteins in the cell. We will review some of the studies that have proposed autophagy as a strategy to reduce the accumulation of polyglutamine-expanded protein aggregates and protect against mutant protein neurotoxicity. We will also discuss some of the currently known mechanisms that induce autophagy, which may be beneficial for the treatment of these and other neurodegenerative disorders.
登录
查看更多内容
AMP激活的蛋白激酶对ULK1（HATG1）的磷酸化将能量传感连接到线粒体。
DOI：
10.1126/science.1196371
发表时间：
2011-01-28
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Egan DF;Shackelford DB;Mihaylova MM;Gelino S;Kohnz RA;Mair W;Vasquez DS;Joshi A;Gwinn DM;Taylor R;Asara JM;Fitzpatrick J;Dillin A;Viollet B;Kundu M;Hansen M;Shaw RJ
通讯作者：
Shaw RJ
影响因子：
7.8
作者：
Degtyarev, Michael;De Maziere, Ann;Orr, Christine;Lin, Jie;Lee, Brian B.;Tien, Janet Y.;Prior, Wei W.;van Dijk, Suzanne;Wu, Hong;Gray, Daniel C.;Davis, David P.;Stern, Howard M.;Murray, Lesley J.;Hoeflich, Klaus P.;Klumperman, Judith;Friedman, Lori S.;Lin, Kui
通讯作者：
Lin, Kui
影响因子：
64.5
作者：
Cárdenas C;Miller RA;Smith I;Bui T;Molgó J;Müller M;Vais H;Cheung KH;Yang J;Parker I;Thompson CB;Birnbaum MJ;Hallows KR;Foskett JK
通讯作者：
Foskett JK
影响因子：
12.4
作者：
Criollo, A.;Maiuri, M. C.;Kroemer, G.
通讯作者：
Kroemer, G.
影响因子：
4.8
作者：
Carmichael, J;Sugars, KL;Rubinsztein, DC
通讯作者：
Rubinsztein, DC