Inflammasome links traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease.

IF 5.9 2区 医学 Q2 CELL BIOLOGY
Neural Regeneration Research Pub Date : 2025-06-01 Epub Date: 2024-07-10 DOI:10.4103/NRR.NRR-D-24-00107
Gabriela Seplovich, Yazan Bouchi, Juan Pablo de Rivero Vaccari, Jennifer C Munoz Pareja, Andrew Reisner, Laura Blackwell, Yehia Mechref, Kevin K Wang, J Adrian Tyndall, Binu Tharakan, Firas Kobeissy
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引用次数: 0

Abstract

Traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease are three distinct neurological disorders that share common pathophysiological mechanisms involving neuroinflammation. One sequela of neuroinflammation includes the pathologic hyperphosphorylation of tau protein, an endogenous microtubule-associated protein that protects the integrity of neuronal cytoskeletons. Tau hyperphosphorylation results in protein misfolding and subsequent accumulation of tau tangles forming neurotoxic aggregates. These misfolded proteins are characteristic of traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease and can lead to downstream neuroinflammatory processes, including assembly and activation of the inflammasome complex. Inflammasomes refer to a family of multimeric protein units that, upon activation, release a cascade of signaling molecules resulting in caspase-induced cell death and inflammation mediated by the release of interleukin-1β cytokine. One specific inflammasome, the NOD-like receptor protein 3, has been proposed to be a key regulator of tau phosphorylation where it has been shown that prolonged NOD-like receptor protein 3 activation acts as a causal factor in pathological tau accumulation and spreading. This review begins by describing the epidemiology and pathophysiology of traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease. Next, we highlight neuroinflammation as an overriding theme and discuss the role of the NOD-like receptor protein 3 inflammasome in the formation of tau deposits and how such tauopathic entities spread throughout the brain. We then propose a novel framework linking traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease as inflammasome-dependent pathologies that exist along a temporal continuum. Finally, we discuss potential therapeutic targets that may intercept this pathway and ultimately minimize long-term neurological decline.

炎症体与创伤性脑损伤、慢性创伤性脑病和阿尔茨海默病有关。
创伤性脑损伤、慢性创伤性脑病和阿尔茨海默病是三种截然不同的神经系统疾病,它们的共同病理生理机制都涉及神经炎症。神经炎症的后遗症之一是 tau 蛋白病理性过度磷酸化,这是一种内源性微管相关蛋白,可保护神经元细胞骨架的完整性。Tau 蛋白过度磷酸化会导致蛋白质错误折叠,随后 Tau 蛋白缠结累积形成神经毒性聚集体。这些错误折叠的蛋白质是创伤性脑损伤、慢性创伤性脑病和阿尔茨海默病的特征,可导致下游神经炎症过程,包括炎性体复合体的组装和激活。炎症小体指的是一系列多聚蛋白单元,它们在激活后会释放一连串信号分子,导致卡巴酶诱导的细胞死亡和白细胞介素-1β细胞因子介导的炎症。一种特殊的炎性体--NOD 样受体蛋白 3--被认为是 tau 磷酸化的关键调节因子,有研究表明,NOD 样受体蛋白 3 的长期激活是病理 tau 累积和扩散的诱因。本综述首先介绍了创伤性脑损伤、慢性创伤性脑病和阿尔茨海默病的流行病学和病理生理学。接下来,我们强调神经炎症是压倒一切的主题,并讨论了 NOD 样受体蛋白 3 炎性体在形成 tau 沉积物中的作用,以及这种 tau 病理实体如何在大脑中扩散。然后,我们提出了一个新的框架,将创伤性脑损伤、慢性创伤性脑病和阿尔茨海默病作为炎性体依赖性病症联系起来,这些病症在时间上具有连续性。最后,我们讨论了可能拦截这一途径并最终最大限度地减少长期神经功能衰退的潜在治疗目标。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Neural Regeneration Research
Neural Regeneration Research CELL BIOLOGY-NEUROSCIENCES
CiteScore
8.00
自引率
9.80%
发文量
515
审稿时长
1.0 months
期刊介绍: Neural Regeneration Research (NRR) is the Open Access journal specializing in neural regeneration and indexed by SCI-E and PubMed. The journal is committed to publishing articles on basic pathobiology of injury, repair and protection to the nervous system, while considering preclinical and clinical trials targeted at improving traumatically injuried patients and patients with neurodegenerative diseases.
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