Neural Regeneration Research ›› 2024, Vol. 19 ›› Issue (9): 1890-1898.doi: 10.4103/1673-5374.390964

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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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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