Cuanalo-Contreras Karina, Mukherjee Abhisek, Soto Claudio
Mitchell Center for Alzheimer's Disease and Related Brain Disorders, Department of Neurology, University of Texas Houston Medical School, Houston, TX 77030, USA ; Benemerita Universidad Autonoma de Puebla, 72160 Puebla, Mexico.
Mitchell Center for Alzheimer's Disease and Related Brain Disorders, Department of Neurology, University of Texas Houston Medical School, Houston, TX 77030, USA.
Int J Cell Biol. 2013;2013:638083. doi: 10.1155/2013/638083. Epub 2013 Nov 17.
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.
蛋白质的错误折叠、聚集和组织蓄积是多种慢性疾病中的常见现象，即所谓的蛋白质错误折叠疾病。这些疾病中的许多都与衰老有关，但这种关联的机制尚不清楚。最近的证据表明，蛋白质聚集体的形成和蓄积可能是正常衰老过程中经常发生的一个过程，但蛋白质错误折叠是衰老的原因还是结果尚不清楚。为了对抗这些错误折叠聚集体的形成，细胞已经发展出复杂且互补的途径来维持蛋白质稳态。这些保护途径包括未折叠蛋白反应、泛素蛋白酶体系统、自噬以及将受损蛋白质包裹在聚集体中。在本文中，我们综述了关于蛋白质错误折叠在疾病和衰老中的作用的现有知识，以及蛋白质稳态细胞途径缺陷在这些过程中的影响。进一步了解蛋白质错误折叠和天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乃至衰老本身的新策略。
