Cells invest in an extensive network of factors to maintain protein homeostasis (proteostasis) and prevent the accumulation of potentially toxic protein aggregates. This proteostasis network (PN) comprises the machineries for the biogenesis, folding, conformational maintenance, and degradation of proteins with molecular chaperones as central coordinators. Here, we review recent progress in understanding the modular architecture of the PN in mammalian cells and how it is modified during cell differentiation. We discuss the capacity and limitations of the PN in maintaining proteome integrity in the face of proteotoxic stresses, such as aggregate formation in neurodegenerative diseases. Finally, we outline various pharmacological interventions to ameliorate proteostasis imbalance.

中文翻译：

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Proteostasis 网络的功能模块。

细胞投资于广泛的因子网络，以维持蛋白质稳态（蛋白质稳态）并防止潜在有毒蛋白质聚集体的积累。该蛋白质稳态网络 (PN) 包括以分子伴侣作为中心协调器的蛋白质的生物发生、折叠、构象维持和降解机制。在这里，我们回顾了在理解哺乳动物细胞中 PN 的模块化结构以及它在细胞分化过程中如何被修改方面的最新进展。我们讨论了 PN 在面对蛋白质毒性压力（例如神经退行性疾病中的聚集体形成）时维持蛋白质组完整性的能力和局限性。最后，我们概述了改善蛋白质稳态失衡的各种药理学干预措施。