Proteasomal dysfunction in aging and Huntington disease.
Proteasomal dysfunction in aging and Huntington disease.
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DOI：
10.1016/j.nbd.2010.11.018
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发表时间：
2011-07
影响因子：
6.1
通讯作者：
Li, Shihua
中科院分区：
文献类型：
--
作者：
Li, Xiao-Jiang;Li, Shihua
蛋白质降解在许多细胞功能中起着核心作用。错误折叠和受损的蛋白质从细胞中被去除，以避免毒性。真核细胞有两条主要的途径来清除错误折叠或毒性蛋白：泛素-蛋白酶体途径和自噬-溶酶体途径。泛素-蛋白酶体系统（UPS）普遍存在于细胞质、细胞核和各种亚细胞区域，而自噬主要在细胞质中起作用。UPS的活性通常保持在高水平，而基础自噬在细胞中组成性地以低水平发生，以执行稳态功能。由于UPS在细胞核中的存在，UPS功能对于清除细胞核中错误折叠的蛋白质可能更重要。多聚谷氨酰胺疾病，包括亨廷顿病（HD），表现出年龄依赖性神经症状和通常在细胞核中发现的错误折叠蛋白的积累。HD中的选择性神经病理学也被发现与疾病蛋白亨廷顿蛋白在神经元细胞中的优先积累有关。虽然UPS对于清除突变的亨廷顿蛋白很重要，但仍不清楚衰老或HD是否影响神经元UPS清除有毒和错误折叠蛋白的能力。本文就UPS功能与衰老及亨廷顿病的关系作一综述。我们还讨论了研究结果表明，老化是一个更重要的因素，可以产生负面影响的UPS的功能。
Protein degradation plays a central role in many cellular functions. Misfolded and damaged proteins are removed from the cells to avoid toxicity. Eukaryotic cells have two main routes for clearing misfolded or toxic proteins: the ubiquitin-proteasome and autophagy-lysosome pathways. The ubiquitin-proteasome system (UPS) is ubiquitously present in the cytoplasm, nucleus, and various subcellular regions whereas autophagy predominantly functions in the cytoplasm. The activity of the UPS often remains at a high level, whereas basal autophagy constitutively occurs at low levels in cells for the performance of homeostatic functions. Because of the presence of the UPS in the nucleus, the UPS function may be more important for clearing misfolded proteins in the nucleus. Polyglutamine diseases, including Huntington disease (HD), show the age-dependent neurological symptoms and the accumulation of misfolded proteins that are often found in the nucleus. The selective neuropathology in HD is also found to associate with the preferential accumulation of the disease protein huntingtin in neuronal cells. Although it is clear that the UPS is important for clearing mutant huntingtin, it remains unclear whether aging or HD affects the capacity of neuronal UPS to remove toxic and misfolded proteins. In this review, we focus on the relationship between the UPS function and aging as well as Huntington disease. We also discuss findings that suggest that aging is a more important factor that can negatively impact the function of the UPS.
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DOI：
10.1083/jcb.141.5.1097
发表时间：
1998-06-01
期刊：
The Journal of cell biology
影响因子：
--
作者：
Hackam AS;Singaraja R;Wellington CL;Metzler M;McCutcheon K;Zhang T;Kalchman M;Hayden MR
通讯作者：
Hayden MR
影响因子：
16
作者：
Benaroudj, N;Zwickl, P;Goldberg, AL
通讯作者：
Goldberg, AL
影响因子：
16
作者：
Bennett, EJ;Bence, NF;Kopito, RR
通讯作者：
Kopito, RR
影响因子：
64.8
作者：
Bennett, Eric J.;Shaler, Thomas A.;Kopito, Ron R.
通讯作者：
Kopito, Ron R.
影响因子：
56.9
作者：
CHAU, V;TOBIAS, JW;VARSHAVSKY, A
通讯作者：
VARSHAVSKY, A