Department of Cellular Biochemistry, Max Planck Institute of Biochemistry, Am Klopferspitz 18, 82152 Martinsried, Germany.
Cold Spring Harb Perspect Biol. 2020 Jan 2;12(1):a033951. doi: 10.1101/cshperspect.a033951.
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.
细胞投入大量的因子来维持蛋白质的平衡（稳态）和防止潜在有毒的蛋白质聚集物的积累。这个蛋白质稳态网络（PN）包含了蛋白质的生物发生、折叠、构象维持和降解的机制，以分子伴侣作为中央协调器。在这里，我们回顾了近年来对哺乳动物细胞中 PN 的模块化结构的理解的进展，以及它在细胞分化过程中是如何被修饰的。我们讨论了 PN 在面对蛋白质毒性应激时，如神经退行性疾病中的聚集体形成，维持蛋白质组完整性的能力和局限性。最后，我们概述了各种改善蛋白质平衡失调的药理学干预措施。
