Department of Biochemistry and Molecular Genetics, American University of Beirut, Beirut, Lebanon.
Department of Biochemistry and Molecular Genetics, American University of Beirut, Beirut, Lebanon; Program for Interdisciplinary Neuroscience, Department of Child Health, School of Medicine, University of Missouri, USA.
Neurosci Biobehav Rev. 2023 Jan;144:104969. doi: 10.1016/j.neubiorev.2022.104969. Epub 2022 Nov 22.
Given the ambiguity surrounding traumatic brain injury (TBI) pathophysiology and the lack of any Food and Drug Administration (FDA)-approved neurotherapeutic drugs, there is an increasing need to better understand the mechanisms of TBI. Recently, the roles of inflammasomes have been highlighted as both potential therapeutic targets and diagnostic markers in different neurodegenerative disorders. Indeed, inflammasome activation plays a pivotal function in the central nervous system (CNS) response to many neurological conditions, as well as to several neurodegenerative disorders, specifically, TBI. This comprehensive review summarizes and critically discusses the mechanisms that govern the activation and assembly of inflammasome complexes and the major methods used to study inflammasome activation in TBI and its implication for other neurodegenerative disorders. Also, we will review how inflammasome activation is critical in CNS homeostasis and pathogenesis, and how it can impact chronic TBI sequalae and increase the risk of developing neurodegenerative diseases. Additionally, we discuss the recent updates on inflammasome-related biomarkers and the potential to utilize inflammasomes as putative therapeutic targets that hold the potential to better diagnose and treat subjects with TBI.
鉴于创伤性脑损伤 (TBI) 发病机制的不明确性以及缺乏任何获得食品和药物管理局 (FDA) 批准的神经治疗药物，人们越来越需要更好地了解 TBI 的机制。最近，炎症小体的作用已被强调为不同神经退行性疾病的潜在治疗靶点和诊断标志物。事实上，炎症小体的激活在中枢神经系统 (CNS) 对许多神经疾病以及几种神经退行性疾病（特别是 TBI）的反应中起着关键作用。这篇综述总结并批判性地讨论了调节炎症小体复合物激活和组装的机制，以及用于研究 TBI 中炎症小体激活及其对其他神经退行性疾病的影响的主要方法。此外，我们将回顾炎症小体激活在 CNS 动态平衡和发病机制中的重要性，以及它如何影响慢性 TBI 后遗症并增加患神经退行性疾病的风险。此外，我们还讨论了炎症小体相关生物标志物的最新进展，以及将炎症小体用作有希望的治疗靶点的潜力，这可能有助于更好地诊断和治疗 TBI 患者。
