Department of Cellular Biochemistry, Max Planck Institute of Biochemistry, Martinsried, Germany
Department of Cellular Biochemistry, Max Planck Institute of Biochemistry, Martinsried, Germany.
J Cell Biol. 2018 Jan 2;217(1):51-63. doi: 10.1083/jcb.201709072. Epub 2017 Nov 10.
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.
确保细胞蛋白质的内稳态，即蛋白质稳态，需要精确控制蛋白质的合成、折叠、构象维持和降解。一个复杂而适应性的蛋白质稳态网络与不同类别的分子伴侣及其调节剂协调这些过程，它们是主要参与者。该网络旨在确保细胞拥有所需的蛋白质，同时最大限度地减少与年龄相关的蛋白质病相关的错误折叠或聚集事件，包括神经退行性疾病，如阿尔茨海默病和帕金森病。现在很清楚的是，细胞维持蛋白质稳态的能力在衰老过程中会下降，使机体易患这些疾病。在这里，我们根据最近的研究讨论主要的蛋白质稳态途径，这些研究表明，它们随年龄增长而失效既可以导致疾病，也可以是疾病的结果。我们考虑了不同的调节蛋白质稳态能力的策略，这可能有助于为神经退行性疾病和其他与年龄相关的疾病开发急需的疗法。
