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NLRP1 Inflammasomes: A Potential Target for the Treatment of Several Types of Brain Injury.
Frontiers in Immunology ( IF 5.7 ) Pub Date : 2022-05-30 , DOI: 10.3389/fimmu.2022.863774
Liang Mi 1, 2 , Xiaobin Min 1, 3 , Yan Chai 2 , Jianning Zhang 1, 2 , Xin Chen 1, 2
Affiliation  

NOD-like receptor (NLR) family pyrin domain-containing 1 (NLRP1) is a member of the NLR family. The NLRP1 inflammasome consists of the NLRP1 protein, the adaptor protein apoptosis-associated speck-like protein containing a CARD domain, and the effector molecule pro-caspase-1. When stimulated, the inflammasome initiates the cleavage of pro-caspase-1 and converts it into its active form, caspase-1; then, caspase-1 facilitates the cleavage of the proinflammatory cytokines interleukin-1β and interleukin-18 into their active and secreted forms. In addition, caspase-1 also mediates the cleavage of gasdermin D, which leads to pyroptosis, an inflammatory form of cell death. Pathological events that damage the brain and result in neuropathological conditions can generally be described as brain injury. Neuroinflammation, especially that driven by NLRP1, plays a considerable role in the pathophysiology of brain injury, such as early brain injury (EBI) of subarachnoid hemorrhage, ischemic brain injury during stroke, and traumatic brain injury (TBI). In this article, a thorough overview of NLRP1 is presented, including its structure, mechanism of activation, and role in neuroinflammation. We also present recent studies on NLRP1 as a target for the treatment of EBI, ischemic brain injury, TBI, and other types of brain injury, thus highlighting the perspective of NLRP1 as an effective mediator of catastrophic brain injury.

中文翻译:

NLRP1 炎症小体:治疗多种脑损伤的潜在靶点。

NOD 样受体 (NLR) 家族含有 pyrin 结构域的 1 (NLRP1) 是 NLR 家族的成员。NLRP1 炎性体由 NLRP1 蛋白、含有 CARD 结构域的衔接蛋白凋亡相关斑点样蛋白和效应分子 pro-caspase-1 组成。当受到刺激时,炎症小体启动 pro-caspase-1 的切割并将其转化为活性形式 caspase-1;然后,caspase-1 促进促炎细胞因子 interleukin-1β 和 interleukin-18 裂解为它们的活性和分泌形式。此外,caspase-1 还介导 gasdermin D 的裂解,从而导致细胞焦亡,这是一种炎症性细胞死亡形式。损害大脑并导致神经病理状况的病理事件通常可以描述为脑损伤。神经炎症,尤其是由 NLRP1 驱动的,在蛛网膜下腔出血的早期脑损伤(EBI)、中风时的缺血性脑损伤和外伤性脑损伤(TBI)等脑损伤的病理生理学中起重要作用。本文对 NLRP1 进行了全面概述,包括其结构、激活机制以及在神经炎症中的作用。我们还介绍了最近关于 NLRP1 作为治疗 EBI、缺血性脑损伤、TBI 和其他类型脑损伤的靶点的研究,从而突出了 NLRP1 作为灾难性脑损伤的有效介质的前景。激活机制,以及在神经炎症中的作用。我们还介绍了最近关于 NLRP1 作为治疗 EBI、缺血性脑损伤、TBI 和其他类型脑损伤的靶点的研究,从而突出了 NLRP1 作为灾难性脑损伤的有效介质的前景。激活机制,以及在神经炎症中的作用。我们还介绍了最近关于 NLRP1 作为治疗 EBI、缺血性脑损伤、TBI 和其他类型脑损伤的靶点的研究,从而突出了 NLRP1 作为灾难性脑损伤的有效介质的前景。
更新日期:2022-05-30
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