Pathways of cellular proteostasis in aging and disease.
Pathways of cellular proteostasis in aging and disease.
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DOI：
10.1083/jcb.201709072
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发表时间：
2018-01-02
期刊：
影响因子：
--
通讯作者：
Hartl FU
中科院分区：
文献类型：
--
作者：
Klaips CL;Jayaraj GG;Hartl FU
Klaips等人概述了细胞蛋白质稳态或蛋白质稳态的途径和分子机制，并讨论了衰老过程中蛋白质稳态的下降如何导致疾病。确保细胞蛋白质稳态或蛋白质稳态需要精确控制蛋白质合成、折叠、构象维持和降解。一个复杂的和适应性的蛋白质稳态网络协调这些过程与不同类别的分子伴侣和他们的监管机构发挥主要作用。该网络用于确保细胞具有它们所需的蛋白质，同时最大限度地减少错误折叠或聚集事件，这些事件是年龄相关蛋白质病的标志，包括神经退行性疾病，如阿尔茨海默病和帕金森病。现在很清楚，细胞维持蛋白质稳态的能力在衰老过程中会下降，使生物体对这些病理学易感。在这里，我们讨论了主要的蛋白质代谢途径，根据最近的研究表明，他们的年龄依赖性故障可以有助于和导致疾病。我们考虑不同的策略来调节蛋白质稳态能力，这可能有助于开发神经退行性疾病和其他年龄依赖性病理学急需的疗法。
Klaips et al. outline the pathways and molecular mechanisms of cellular protein homeostasis, or proteostasis, and discuss how a decline in proteostasis during aging contributes to disease. Ensuring cellular protein homeostasis, or proteostasis, requires precise control of protein synthesis, folding, conformational maintenance, and degradation. A complex and adaptive proteostasis network coordinates these processes with molecular chaperones of different classes and their regulators functioning as major players. This network serves to ensure that cells have the proteins they need while minimizing misfolding or aggregation events that are hallmarks of age-associated proteinopathies, including neurodegenerative disorders such as Alzheimer’s and Parkinson’s diseases. It is now clear that the capacity of cells to maintain proteostasis undergoes a decline during aging, rendering the organism susceptible to these pathologies. Here we discuss the major proteostasis pathways in light of recent research suggesting that their age-dependent failure can both contribute to and result from disease. We consider different strategies to modulate proteostasis capacity, which may help develop urgently needed therapies for neurodegeneration and other age-dependent pathologies.
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