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针对 NLRP3 炎性小体作为炎症性肠病的新治疗靶点。

Targeting the NLRP3 inflammasome as new therapeutic avenue for inflammatory bowel disease.

机构信息

State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, PR China; Institute of Chinese Medical Sciences and State Key Laboratory of Quality Research in Chinese Medicine, University of Macau, Avenida da Universidade, Taipa, Macao SAR, PR China.

Institute of Chinese Medical Sciences and State Key Laboratory of Quality Research in Chinese Medicine, University of Macau, Avenida da Universidade, Taipa, Macao SAR, PR China.

出版信息

Biomed Pharmacother. 2021 Jun;138:111442. doi: 10.1016/j.biopha.2021.111442. Epub 2021 Mar 2.

Abstract

The incidence and prevalence of inflammatory bowel disease (IBD) are increasing worldwide. Current approved medication for IBD treatment in the clinic mainly includes corticosteroids and neutralization antibodies to pro-inflammatory cytokines. However, drug resistance and severe side effect hinder long-term efficacy of these agents. The NOD-like receptor family pyrin domain containing protein 3 (NLRP3) is exclusively expressed in several inflammatory and autoimmune diseases. Excessive expression, aberrant activation, polymorphism, and gain-of-function mutation of the NLRP3 inflammasome contribute to IBD pathogenesis. In this article, we summarize the regulatory factors to NLRP3, and review recently developed NLRP3 inhibitors and their preclinical and clinical applications in treating inflammatory and autoimmune diseases. We present our views on the therapeutic potential of NLRP3 inhibitors as emerging therapeutic avenue for IBD.

摘要

炎症性肠病(IBD)的发病率和患病率在全球范围内呈上升趋势。目前临床上用于治疗 IBD 的药物主要包括皮质类固醇和中和促炎细胞因子的单克隆抗体。然而,药物耐药性和严重的副作用阻碍了这些药物的长期疗效。NOD 样受体家族富含吡咯烷域蛋白 3(NLRP3)仅在几种炎症性和自身免疫性疾病中表达。NLRP3 炎性小体的过度表达、异常激活、多态性和功能获得性突变导致 IBD 的发病机制。本文总结了 NLRP3 的调控因子,并综述了最近开发的 NLRP3 抑制剂及其在治疗炎症性和自身免疫性疾病中的临床前和临床应用。我们对 NLRP3 抑制剂作为治疗 IBD 的新兴治疗途径的治疗潜力提出了我们的看法。

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