Abstract：
Proteostasis is essential for normal function of proteins and vital for cellular health and survival. Proteostasis encompasses all stages in the \"life\" of a protein, that is, from translation to functional performance and, ultimately, to degradation. Proteins need native conformations for function and in the presence of multiple types of stress, their misfolding and aggregation can occur. A coordinated network of proteins is at the core of proteostasis in cells. Among these, chaperones are required for maintaining the integrity of protein conformations by preventing misfolding and aggregation and guide those with abnormal conformation to degradation. The ubiquitin-proteasome system (UPS) and autophagy are major cellular pathways for degrading proteins. Although failure or decreased functioning of components of this network can lead to proteotoxicity and disease, like neuron degenerative diseases, underlying factors are not completely understood. Accumulating misfolded and aggregated proteins are considered major pathomechanisms of neurodegeneration. In this chapter, we have described the components of three major branches required for proteostasis-chaperones, UPS and autophagy, the mechanistic basis of their function, and their potential for protection against various neurodegenerative conditions, like Alzheimer\'s, Parkinson\'s, and Huntington\'s disease. The modulation of various proteostasis network proteins, like chaperones, E3 ubiquitin ligases, proteasome, and autophagy-associated proteins as therapeutic targets by small molecules as well as new and unconventional approaches, shows promise.
摘要：
蛋白质停滞对蛋白质的正常功能至关重要，对细胞健康和生存至关重要。蛋白质停滞包括蛋白质“生命”的所有阶段，也就是说,从翻译到功能性能，最终,退化。蛋白质需要天然构象的功能和存在多种类型的应激，它们的错误折叠和聚集可能会发生。蛋白质的协调网络是细胞中蛋白质停滞的核心。其中,分子伴侣通过防止错误折叠和聚集来维持蛋白质构象的完整性，并引导那些具有异常构象的降解。泛素-蛋白酶体系统（UPS）和自噬是降解蛋白质的主要细胞途径。尽管该网络的组件的故障或功能下降会导致蛋白质毒性和疾病，像神经元退行性疾病一样，潜在因素还没有完全理解。积累错误折叠和聚集的蛋白质被认为是神经变性的主要病理机制。在这一章中,我们已经描述了蛋白质稳定所需的三个主要分支的组成部分-伴侣，UPS和自噬，它们功能的机械基础，以及它们预防各种神经退行性疾病的潜力，像老年痴呆症，帕金森,和亨廷顿病。调节各种蛋白稳定网络蛋白，像监护人一样，E3泛素连接酶，蛋白酶体,和自噬相关蛋白通过小分子以及新的和非常规的方法作为治疗靶点，显示承诺。
