The biology of proteostasis in aging and disease.
The biology of proteostasis in aging and disease.
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DOI：
10.1146/annurev-biochem-060614-033955
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发表时间：
2015
影响因子：
16.6
通讯作者：
Morimoto RI
中科院分区：
文献类型：
--
作者：
Labbadia J;Morimoto RI
蛋白质稳态的丧失（蛋白质稳态）是衰老和疾病的共同特征，其特征在于各种组织中出现非天然蛋白质聚集体。蛋白质聚集通常被蛋白质稳态网络（PN）抑制，蛋白质稳态网络是以不同方式操作的大分子机器的集合，以维持跨亚细胞区室和组织之间的蛋白质组完整性，以确保健康的寿命。在这里，我们审查的组成，功能和组织特性的PN的背景下，单个细胞和整个生物体，并讨论的机制，其中PN的中断，相关的应激反应途径，有助于疾病的发生和发展。我们探索新出现的证据表明，疾病的易感性产生于PN的组成和活性的早期变化，并提出更完整的理解PN的时间和空间特性将提高我们的能力，开发有效的治疗蛋白质构象疾病。
Loss of protein homeostasis (proteostasis) is a common feature of aging and disease that is characterized by the appearance of nonnative protein aggregates in various tissues. Protein aggregation is routinely suppressed by the proteostasis network (PN), a collection of macromolecular machines that operate in diverse ways to maintain proteome integrity across subcellular compartments and between tissues to ensure a healthy life span. Here, we review the composition, function, and organizational properties of the PN in the context of individual cells and entire organisms and discuss the mechanisms by which disruption of the PN, and related stress response pathways, contributes to the initiation and progression of disease. We explore emerging evidence that disease susceptibility arises from early changes in the composition and activity of the PN and propose that a more complete understanding of the temporal and spatial properties of the PN will enhance our ability to develop effective treatments for protein conformational diseases.