Role of protein misfolding and proteostasis deficiency in protein misfolding diseases and aging.
Role of protein misfolding and proteostasis deficiency in protein misfolding diseases and aging.
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DOI：
10.1155/2013/638083
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发表时间：
2013
影响因子：
--
通讯作者：
Soto C
中科院分区：
文献类型：
--
作者：
Cuanalo-Contreras K;Mukherjee A;Soto C
蛋白质的错误折叠、聚集和组织积累是多种慢性疾病的常见事件，称为蛋白质错误折叠疾病。其中许多疾病与衰老有关，但这种联系的机制尚不清楚。最近的证据表明，蛋白质聚集体的形成和积累可能是正常衰老过程中经常发生的过程，但尚不清楚蛋白质错误折叠是衰老的原因还是结果。为了对抗这些错误折叠聚集体的形成，细胞开发了复杂且互补的途径，旨在维持蛋白质稳态。这些保护途径包括未折叠的蛋白质反应、泛素蛋白酶体系统、自噬以及聚集体中受损蛋白质的封装。在本文中，我们回顾了有关蛋白质错误折叠在疾病和衰老中的作用以及这些过程中蛋白质稳态细胞途径缺陷的影响的最新知识。进一步了解蛋白质错误折叠和自然防御途径所涉及的机制可能会带来治疗年龄依赖性蛋白质错误折叠疾病以及衰老本身的新策略。
The misfolding, aggregation, and tissue accumulation of proteins are common events in diverse chronic diseases, known as protein misfolding disorders. Many of these diseases are associated with aging, but the mechanism for this connection is unknown. Recent evidence has shown that the formation and accumulation of protein aggregates may be a process frequently occurring during normal aging, but it is unknown whether protein misfolding is a cause or a consequence of aging. To combat the formation of these misfolded aggregates cells have developed complex and complementary pathways aiming to maintain protein homeostasis. These protective pathways include the unfolded protein response, the ubiquitin proteasome system, autophagy, and the encapsulation of damaged proteins in aggresomes. In this paper we review the current knowledge on the role of protein misfolding in disease and aging as well as the implication of deficiencies in the proteostasis cellular pathways in these processes. It is likely that further understanding of the mechanisms involved in protein misfolding and the natural defense pathways may lead to novel strategies for treatment of age-dependent protein misfolding disorders and perhaps aging itself.