Smolen Paul, Dash Pramod K, Redell John B
Department of Neurobiology and Anatomy, McGovern Medical School, University of Texas Health Science Center, Houston, TX, United States.
Front Neurosci. 2023 Sep 19;17:1259405. doi: 10.3389/fnins.2023.1259405. eCollection 2023.
Epidemiological studies have shown that traumatic brain injury (TBI) increases the risk for developing neurodegenerative diseases (NDs). However, molecular mechanisms that underlie this risk are largely unidentified. TBI triggers widespread epigenetic modifications. Similarly, NDs such as Alzheimer's or Parkinson's are associated with numerous epigenetic changes. Although epigenetic changes can persist after TBI, it is unresolved if these modifications increase the risk of later ND development and/or dementia. We briefly review TBI-related epigenetic changes, and point out putative feedback loops that might contribute to long-term persistence of some modifications. We then focus on evidence suggesting persistent TBI-associated epigenetic changes may contribute to pathological processes (e.g., neuroinflammation) which may facilitate the development of specific NDs - Alzheimer's disease, Parkinson's disease, or chronic traumatic encephalopathy. Finally, we discuss possible directions for TBI therapies that may help prevent or delay development of NDs.
流行病学研究表明，创伤性脑损伤（TBI）会增加患神经退行性疾病（NDs）的风险。然而，这种风险背后的分子机制在很大程度上尚不清楚。TBI会引发广泛的表观遗传修饰。同样，诸如阿尔茨海默病或帕金森病等神经退行性疾病与众多表观遗传变化有关。尽管TBI后表观遗传变化可能持续存在，但这些修饰是否会增加后期发生神经退行性疾病和/或痴呆的风险仍未得到解决。我们简要回顾与TBI相关的表观遗传变化，并指出可能导致某些修饰长期持续存在的假定反馈回路。然后，我们重点关注证据，表明与TBI相关的持续表观遗传变化可能促成病理过程（如神经炎症），这可能会促进特定神经退行性疾病——阿尔茨海默病、帕金森病或慢性创伤性脑病的发展。最后，我们讨论了TBI治疗的可能方向，这些方向可能有助于预防或延缓神经退行性疾病的发展。
