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.

TBI 的后果与急性应激反应和不溶性蛋白质聚集体的积累有关。即使在 TBI 的症状得到解决后，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展。导致不健康的大脑老化的精确分子级联在很大程度上仍然未知。在这篇综述中，我们讨论了蛋白质抑制功能障碍作为导致 TBI 后加速大脑衰老的一种收敛机制。我们检查来自人体组织和体内的证据动物模型，涵盖衰老和损伤背景。我们得出结论，TBI 对蛋白质稳定机制具有持续的衰弱作用，这可能导致损伤后观察到的衰老的加速病理和认知特征。