脑损伤与衰老的协同作用：蛋白稳态功能障碍的共同机制。
Synergistic effects of brain injury and aging: common mechanisms of proteostatic dysfunction.
机构信息
Department of Biology, University of Pennsylvania, Philadelphia, PA 19104, USA.
Department of Biology, University of Pennsylvania, Philadelphia, PA 19104, USA.
出版信息
Trends Neurosci. 2021 Sep;44(9):728-740. doi: 10.1016/j.tins.2021.06.003. Epub 2021 Jul 20.
Abstract
The aftermath of TBI is associated with an acute stress response and the accumulation of insoluble protein aggregates. Even after the symptoms of TBI are resolved, insidious molecular processes continue to develop, which often ultimately result in the development of age-associated neurodegenerative disorders. The precise molecular cascades that drive unhealthy brain aging are still largely unknown. In this review, we discuss proteostatic dysfunction as a converging mechanism contributing to accelerated brain aging after TBI. We examine evidence from human tissue and in vivo animal models, spanning both the aging and injury contexts. We conclude that TBI has a sustained debilitating effect on the proteostatic machinery, which may contribute to the accelerated pathological and cognitive hallmarks of aging that are observed following injury.
摘要
TBI 后会引起急性应激反应和不溶性蛋白聚集体的积累。即使 TBI 的症状得到缓解，隐匿的分子过程仍在继续发展，这通常最终导致与年龄相关的神经退行性疾病的发生。导致不健康脑衰老的确切分子级联反应在很大程度上仍不清楚。在这篇综述中，我们讨论了作为导致 TBI 后大脑加速衰老的汇聚机制的蛋白质稳态失调。我们检查了来自人类组织和体内动物模型的证据，涵盖了衰老和损伤两个方面。我们的结论是，TBI 对蛋白质稳态机制有持续的削弱作用，这可能导致损伤后观察到的与年龄相关的病理和认知特征的加速。
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