Geriatric Research Education and Clinical Center, Pittsburgh VA Healthcare System, Pittsburgh, PA, USA; Department of Neurology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Geriatric Research Education and Clinical Center, Pittsburgh VA Healthcare System, Pittsburgh, PA, USA; Department of Neurology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Neuropharmacology. 2019 Feb;145(Pt B):160-176. doi: 10.1016/j.neuropharm.2018.06.021. Epub 2018 Jun 20.
Traumatic brain injury (TBI) is a risk factor for development of chronic neurodegenerative disorders later in life. This review summarizes the current knowledge and concepts regarding the connection between long-term consequences of TBI and aging-associated neurodegenerative disorders including Alzheimer's disease (AD), chronic traumatic encephalopathy (CTE), and Parkinsonism, with implications for novel therapy targets. Several aggregation-prone proteins such as the amyloid-beta (Aβ) peptides, tau proteins, and α-synuclein protein are involved in secondary pathogenic cascades initiated by a TBI and are also major building blocks of the hallmark pathological lesions in chronic human neurodegenerative diseases with dementia. Impaired metabolism and degradation pathways of aggregation-prone proteins are discussed as potentially critical links between the long-term aftermath of TBI and chronic neurodegeneration. Utility and limitations of previous and current preclinical TBI models designed to study the link between TBI and chronic neurodegeneration, and promising intervention pharmacotherapies and non-pharmacologic strategies to break this link, are also summarized. Complexity of long-term neuropathological consequences of TBI is discussed, with a goal of guiding future preclinical studies and accelerating implementation of promising therapeutics into clinical trials. This article is part of the Special Issue entitled "Novel Treatments for Traumatic Brain Injury".
创伤性脑损伤（TBI）是日后发生慢性神经退行性疾病的危险因素。这篇综述总结了目前关于 TBI 的长期后果与阿尔茨海默病（AD）、慢性创伤性脑病（CTE）和帕金森病等与衰老相关的神经退行性疾病之间联系的知识和概念，为新的治疗靶点提供了依据。几种易于聚集的蛋白质，如淀粉样β（Aβ）肽、tau 蛋白和α-突触核蛋白，参与由 TBI 引发的继发性致病级联反应，也是慢性人类神经退行性痴呆疾病标志性病理损伤的主要组成部分。聚集倾向蛋白的代谢和降解途径受损被认为是 TBI 长期后果与慢性神经变性之间的潜在关键联系。本文还总结了以前和目前用于研究 TBI 与慢性神经退行性变之间联系的临床前 TBI 模型的实用性和局限性，以及有希望的干预性药物治疗和非药物策略，以打破这种联系。本文还讨论了 TBI 长期神经病理学后果的复杂性，旨在为未来的临床前研究提供指导，并加速有希望的治疗方法进入临床试验。本文是“创伤性脑损伤的新疗法”特刊的一部分。
