Proteostasis and the Aging Proteome in Health and Disease
Proteostasis and the Aging Proteome in Health and Disease
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DOI：
10.1093/gerona/glu049
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发表时间：
2014-06-01
影响因子：
5.1
通讯作者：
Cuervo, Ana Maria
中科院分区：
文献类型：
--
作者：
Morimoto, Richard I.;Cuervo, Ana Maria
蛋白质组的维持对于保持细胞功能以及响应和适应不断变化的环境的能力至关重要。这是由蛋白质稳态网络调节的，蛋白质稳态网络是由分子伴侣和蛋白质清除机制组成的一组专用分子组分，由细胞应激信号传导途径调节，其防止与蛋白质错误折叠相关的毒性和不同亚细胞区室和组织中有毒聚集体的积累。蛋白质稳态网络的效率随着年龄的增长而下降，这种蛋白质稳态的失败被认为是常见的年龄相关人类疾病的基础。目前的进展，在了解的机制和调节蛋白质和不同类型的偏离在这个过程中，在老化已经转向注意力对提供的治疗机会，恢复蛋白质在年龄相关的退行性疾病。在这里，我们讨论了一些尚未解决的问题，需要解决的蛋白质稳态，以提高健康寿命，并减少与持续性蛋白质损伤相关的病理。
The maintenance of the proteome is essential to preserve cell functionality and the ability to respond and adapt to the changing environment. This is regulated by the proteostasis network, a dedicated set of molecular components comprised of molecular chaperones and protein clearance mechanisms, regulated by cell stress signaling pathways, that prevents the toxicity associated with protein misfolding and accumulation of toxic aggregates in different subcellular compartments and tissues. The efficiency of the proteostasis network declines with age and this failure in protein homeostasis has been proposed to underlie the basis of common age-related human disorders. The current advances in the understanding of the mechanisms and regulation of proteostasis and of the different types of digressions in this process in aging have turned the attention toward the therapeutic opportunities offered by the restoration of proteostasis in age-associated degenerative diseases. Here, we discuss some of the unresolved questions on proteostasis that need to be addressed to enhance healthspan and to diminish the pathology associated with persistent protein damage.