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靶向NLRP3炎性小体在神经系统疾病转化治疗中的研究进展

Targeting NLRP3 Inflammasome in Translational Treatment of Nervous System Diseases: An Update.

作者信息

Yu Qingying, Zhao Tingting, Liu Molin, Cao Duo, Li Jiaxin, Li Yanling, Xia Mengyao, Wang Xiaoyu, Zheng Tingting, Liu Chuanguo, Mu Xiangyu, Sun Peng

机构信息

School of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, China.

School of Foreign Languages, Shandong University of Traditional Chinese Medicine, Jinan, China.

出版信息

Front Pharmacol. 2021 Aug 30;12:707696. doi: 10.3389/fphar.2021.707696. eCollection 2021.

DOI:10.3389/fphar.2021.707696
PMID:34526897
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8435574/
Abstract

Neuroinflammatory response is the immune response mechanism of the innate immune system of the central nervous system. Both primary and secondary injury can activate neuroinflammatory response. Among them, the nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome plays a key role in the inflammatory response of the central system. Inflammasome is a type of pattern recognition receptor, a cytoplasmic polyprotein complex composed of members of the Nod-like receptor (NLR) family and members of the pyrin and HIN domain (PYHIN) family, which can be affected by a variety of pathogen-related molecular patterns or damage-related molecular patterns are activated. As one of the research hotspots in the field of medical research in recent years, there are increasing researches on immune function abnormalities in the onset of neurological diseases such as depression, AD, ischemic brain injury and cerebral infarction, the NLRP3 inflammasome causes the activated caspase-1 to cleave pre-interleukin-1β and pre-interleukin-18 into mature interleukin-1β and interleukin-18, in turn, a large number of inflammatory factors are produced, which participate in the occurrence and development of the above-mentioned diseases. Targeted inhibition of the activation of inflammasomes can reduce the inflammatory response, promote the survival of nerve cells, and achieve neuroprotective effects. This article reviews NLRP3 inflammasome's role in neurological diseases and related regulatory mechanisms, which providing references for future research in this field.

摘要

神经炎症反应是中枢神经系统固有免疫系统的免疫反应机制。原发性损伤和继发性损伤均可激活神经炎症反应。其中,核苷酸结合寡聚化结构域样受体蛋白3(NLRP3)炎性小体在中枢系统的炎症反应中起关键作用。炎性小体是一种模式识别受体,是由Nod样受体(NLR)家族成员和吡喃素和HIN结构域(PYHIN)家族成员组成的细胞质多蛋白复合物,可受多种病原体相关分子模式或损伤相关分子模式激活。作为近年来医学研究领域的热点之一,关于抑郁症、阿尔茨海默病(AD)、缺血性脑损伤和脑梗死等神经疾病发病过程中免疫功能异常的研究越来越多,NLRP3炎性小体促使活化的半胱天冬酶-1将前白细胞介素-1β和前白细胞介素-18切割成成熟的白细胞介素-1β和白细胞介素-18,进而产生大量炎性因子,参与上述疾病的发生发展。靶向抑制炎性小体的激活可减轻炎症反应,促进神经细胞存活,实现神经保护作用。本文综述了NLRP3炎性小体在神经疾病中的作用及相关调控机制,为该领域未来研究提供参考。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a74/8435574/92179f4872d0/fphar-12-707696-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a74/8435574/cc058f7bd79d/fphar-12-707696-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a74/8435574/4cf280d84a40/fphar-12-707696-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a74/8435574/92179f4872d0/fphar-12-707696-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a74/8435574/cc058f7bd79d/fphar-12-707696-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a74/8435574/4cf280d84a40/fphar-12-707696-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a74/8435574/92179f4872d0/fphar-12-707696-g003.jpg

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