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聚焦NLRP3炎性小体在多发性硬化中的作用:发病机制、诊断与治疗

Focus on the Role of the NLRP3 Inflammasome in Multiple Sclerosis: Pathogenesis, Diagnosis, and Therapeutics.

作者信息

Cui Yueran, Yu Haiyang, Bu Zhongqi, Wen Lulu, Yan Lili, Feng Juan

机构信息

Department of Neurology, Shengjing Hospital of China Medical University, Shenyang, China.

出版信息

Front Mol Neurosci. 2022 May 25;15:894298. doi: 10.3389/fnmol.2022.894298. eCollection 2022.

Abstract

Neuroinflammation is initiated with an aberrant innate immune response in the central nervous system (CNS) and is involved in many neurological diseases. Inflammasomes are intracellular multiprotein complexes that can be used as platforms to induce the maturation and secretion of proinflammatory cytokines and pyroptosis, thus playing a pivotal role in neuroinflammation. Among the inflammasomes, the nucleotide-binding oligomerization domain-, leucine-rich repeat- and pyrin domain-containing 3 (NLRP3) inflammasome is well-characterized and contributes to many neurological diseases, such as multiple sclerosis (MS), Alzheimer's disease (AD), and ischemic stroke. MS is a chronic autoimmune disease of the CNS, and its hallmarks include chronic inflammation, demyelination, and neurodegeneration. Studies have demonstrated a relationship between MS and the NLRP3 inflammasome. To date, the pathogenesis of MS is not fully understood, and clinical studies on novel therapies are still underway. Here, we review the activation mechanism of the NLRP3 inflammasome, its role in MS, and therapies targeting related molecules, which may be beneficial in MS.

摘要

神经炎症始于中枢神经系统(CNS)中异常的先天性免疫反应,并涉及许多神经系统疾病。炎性小体是细胞内的多蛋白复合物,可作为诱导促炎细胞因子成熟和分泌以及细胞焦亡的平台,从而在神经炎症中起关键作用。在炎性小体中,含核苷酸结合寡聚化结构域、富含亮氨酸重复序列和吡啉结构域的3(NLRP3)炎性小体已得到充分表征,并与许多神经系统疾病有关,如多发性硬化症(MS)、阿尔茨海默病(AD)和缺血性中风。MS是一种中枢神经系统的慢性自身免疫性疾病,其特征包括慢性炎症、脱髓鞘和神经退行性变。研究表明MS与NLRP3炎性小体之间存在关联。迄今为止,MS的发病机制尚未完全阐明,针对新疗法的临床研究仍在进行中。在此,我们综述了NLRP3炎性小体的激活机制、其在MS中的作用以及针对相关分子的疗法,这些可能对MS有益。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/13d5/9175009/3cf575a62dbb/fnmol-15-894298-g0001.jpg

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