中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2024, Vol. 19 ›› Issue (9): 1890-1898.doi: 10.4103/1673-5374.390964

• 综述:神经损伤修复保护与再生 • 上一篇    下一篇

小胶质细胞NLRP3炎症小体介导抑郁神经炎症及其治疗策略

  

  • 出版日期:2024-09-15 发布日期:2024-01-25
  • 基金资助:
    浦东新区卫健委卫生计生科学研究项目（PW2020E-4）；上海中医药大学附属曙光医院思明青年基金项目（SGKJ-202119）；上海市2021年“科技创新行动计划”医疗创新研究专项（21Y21920200）；上海市2023年度“科技创新行动计划”启明星项目（扬帆专项）（23YF1418200）；上海市卫生健康委员会基金资助项目（20234Y0294）；上海健康医学院师资人才百人库项目（A1-2601-23-311007-21）；山西省高等学校科技创新计划项目（2021L350）；山西省基础研究计划项目（20210302124194）

Microglial NLRP3 inflammasome-mediated neuroinflammation and therapeutic strategies in depression

Qiuqin Han1, *, #, Wenhui Li1, #, Peiqing Chen1, Lijuan Wang1, Xiwen Bao1, Renyan Huang2, Guobin Liu2, *, Xiaorong Chen3, *   

  1. 1Department of Scientific Research, Shanghai University of Medicine & Health Sciences Affiliated Zhoupu Hospital, Shanghai, China; 2Department of Traditional Chinese Vascular Surgery, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China; 3Department of Physiology, Laboratory of Neurodegenerative Diseases, Changzhi Medical College, Changzhi, Shanxi Province, China
  • Online:2024-09-15 Published:2024-01-25
  • Contact: Xiaorong Chen, PhD, cxr20020532@126.com; Guobin Liu, PhD, drliuguobin@shutcm.edu.cn; Qiuqin Han, PhD, hqq@sumhs.edu.cn.
  • Supported by:
    This work was supported by Health Commission of Pudong New Area Health and Family Planning Scientific Research Project, No. PW2020E-4 (to GL); Siming Youth Fund Project of Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, No. SGKJ-202119 (to RH); Medical Innovation Research Special Project of 2021 “Science and Technology Innovation Action Plan” of Shanghai, No. 21Y21920200 (to GL); Shanghai Rising-Star Program and Shanghai Sailing Program, No. 23YF1418200 (to QH); Shanghai Municipal Health Commission Foundation grant, No. 20234Y0294 (to QH); Hundred Teacher Talent Program of Shanghai University of Medicine and Health Sciences, No. A1-2601-23-311007-21 (to QH); the Scientific and Technological Innovation Program of Higher Education Institution in Shanxi, No. 2021L350 (to XC); the Fundamental Research Program of Shanxi Province, No. 20210302124194 (to XC).

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摘要：

有证据表明，炎症和抑郁之间存在双向关系。由于NLRP3炎症小体的激活与多种神经系统疾病的发病机制密切相关，且在重度抑郁患者中，NLRP3炎症小体显著高表达。因此，了解NLRP3炎症小体介导的神经炎症在抑郁发病机制中的作用将有利于探索未来的治疗策略。此次综述旨在阐明抑郁中导致NLRP3炎症小体激活的机制，并深入了解针对NLRP3炎性小体的治疗策略。此外，文章还概括了针对NLRP3炎症小体的各种治疗策略，包括NLRP3炎性通路抑制剂、天然化合物和其他化合物以及非药物疗法。这些方法在抑郁治疗方面取得了显著效果。最后总结了有关抑郁临床试验中NLRP3炎症小体抑制剂的应用。虽然目前关于NLRP3炎症小体抑制剂在抑郁治疗的临床试验还很少，但该领域的研究已经引起了广泛关注，这为抑郁治疗带来了新希望。因此有必要确定这些方法治疗抑郁的有效性和安全性，这将为临床抑郁治疗开辟新的道路。

https://orcid.org/0009-0008-8311-4527 (Xiaorong Chen); https://orcid.org/0000-0002-3283-4275 (Guobin Liu); https://orcid.org/0000-0001-7060-1459 (Qiuqin Han)

关键词: 抑郁, NLRP3炎症小体, 神经炎症, 小胶质细胞

Abstract: Previous studies have demonstrated a bidirectional relationship between inflammation and depression. Activation of the nucleotide-binding oligomerization domain, leucine-rich repeat, and NLR family pyrin domain-containing 3 (NLRP3) inflammasomes is closely related to the pathogenesis of various neurological diseases. In patients with major depressive disorder, NLRP3 inflammasome levels are significantly elevated. Understanding the role that NLRP3 inflammasome-mediated neuroinflammation plays in the pathogenesis of depression may be beneficial for future therapeutic strategies. In this review, we aimed to elucidate the mechanisms that lead to the activation of the NLRP3 inflammasome in depression as well as to provide insight into therapeutic strategies that target the NLRP3 inflammasome. Moreover, we outlined various therapeutic strategies that target the NLRP3 inflammasome, including NLRP3 inflammatory pathway inhibitors, natural compounds, and other therapeutic compounds that have been shown to be effective in treating depression. Additionally, we summarized the application of NLRP3 inflammasome inhibitors in clinical trials related to depression. Currently, there is a scarcity of clinical trials dedicated to investigating the applications of NLRP3 inflammasome inhibitors in depression treatment. The modulation of NLRP3 inflammasomes in microglia holds promise for the management of depression. Further investigations are necessary to ascertain the efficacy and safety of these therapeutic approaches as potential novel antidepressant treatments.

Key words: depression, microglia, neuroinflammation, NLRP3 inflammasome