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NLRP3炎性小体是围手术期神经认知障碍的一种潜在机制和治疗靶点。

The NLRP3 inflammasome is a potential mechanism and therapeutic target for perioperative neurocognitive disorders.

作者信息

Li Jiayue, Li Li, He Jiannan, Xu Jianhong, Bao Fangping

机构信息

Department of Anesthesiology, The Fourth Affiliated Hospital, International Institutes of Medicine, Zhejiang University School of Medicine, Yiwu, China.

Department of Anesthesiology, The First Affiliated Hospital Zhejiang University School of Medicine, Hangzhou, China.

出版信息

Front Aging Neurosci. 2023 Jan 4;14:1072003. doi: 10.3389/fnagi.2022.1072003. eCollection 2022.

Abstract

Perioperative neurocognitive disorders (PNDs) are frequent complications associated with cognitive impairment during the perioperative period, including acute postoperative delirium and long-lasting postoperative cognitive dysfunction. There are some risk factors for PNDs, such as age, surgical trauma, anesthetics, and the health of the patient, but the underlying mechanism has not been fully elucidated. Pyroptosis is a form of programmed cell death that is mediated by the gasdermin protein and is involved in cognitive dysfunction disorders. The canonical pathway induced by nucleotide oligomerization domain (NOD)-, leucine-rich repeat (LRR)- and pyrin domain-containing protein 3 (NLRP3) inflammasomes contributes to PNDs, which suggests that targeting NLRP3 inflammasomes may be an effective strategy for the treatment of PNDs. Therefore, inhibiting upstream activators and blocking the assembly of the NLRP3 inflammasome may attenuate PNDs. The present review summarizes recent studies and systematically describes the pathogenesis of NLRP3 activation and regulation and potential therapeutics targeting NLRP3 inflammasomes in PNDs patients.

摘要

围手术期神经认知障碍(PNDs)是围手术期与认知功能损害相关的常见并发症,包括急性术后谵妄和长期术后认知功能障碍。PNDs存在一些危险因素,如年龄、手术创伤、麻醉剂和患者健康状况等,但其潜在机制尚未完全阐明。细胞焦亡是一种由gasdermin蛋白介导的程序性细胞死亡形式,与认知功能障碍性疾病有关。由含核苷酸寡聚化结构域(NOD)、富含亮氨酸重复序列(LRR)和pyrin结构域的蛋白3(NLRP3)炎性小体诱导的经典途径与PNDs有关,这表明靶向NLRP3炎性小体可能是治疗PNDs的有效策略。因此,抑制上游激活剂并阻断NLRP3炎性小体的组装可能减轻PNDs。本综述总结了近期研究,并系统描述了NLRP3激活和调控的发病机制以及针对PNDs患者NLRP3炎性小体的潜在治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d8ec/9845955/aa055fc5b663/fnagi-14-1072003-g001.jpg

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