中国药物警戒 ›› 2026, Vol. 23 ›› Issue (9): 1070-1074.
DOI: 10.19803/j.1672-8629.20260314

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小胶质细胞自噬-NLRP3炎症小体轴在帕金森病中的病理机制及靶向药物研究进展

张璇1, 董斌1Δ, 王骞琛2, 陈丽平2, 周玲玉2, 杨珺1#, 闫加庆1,*   

  1. 1国家癌症中心,国家肿瘤临床医学研究中心,中国医学科学院北京协和医学院肿瘤医院药剂科,北京 100021;
    2中国医科大学第一附属医院药剂科,辽宁 沈阳 110001
  • 收稿日期:2026-04-27 出版日期:2026-09-15 发布日期:2026-09-15
  • 通讯作者: *闫加庆,男,博士,副主任药师,神经药理学。E-mail: yanjiaqing@cicams.ac.cn。#为共同通信作者。
  • 作者简介:张璇,女,在读硕士,神经药理学。Δ为并列第一作者。
  • 基金资助:
    北京自然科学基金资助项目（7262183）; 中国药学会医院药学专委会医院药学科研专项（CPA-Z05-ZC-2025002）; 吴阶平医学基金会药物治疗专项科研课题（320.6750.2024-18-4）; 北京医学奖励基金会科学研究基金（YXJL-2024-0000-0113）

Pathological mechanisms of the microglial autophagy-NLRP3 inflammasome axis in Parkinson's disease and research progress in targeted drugs

Zhang Xuan1, Dong Bin1Δ, Wang Qianchen2, Chen Liping2, Zhou Lingyu2, Yang Jun1#, Yan Jiaqing1,*   

  1. 1Department of Pharmacy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China;
    2Department of Pharmacy, the First Affiliated Hospital of China Medical University, Shenyang Liaoning 110001, China
  • Received:2026-04-27 Online:2026-09-15 Published:2026-09-15

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摘要： 目的 阐释小胶质细胞自噬与NLRP3炎症的调控网络,梳理靶向该轴候选药物现状,为帕金森病新型靶向药物开发与临床干预研究提供参考。方法 通过文献调研,系统梳理帕金森病病理机制、NLRP3炎症小体激活通路及细胞自噬调控机制,归纳小胶质细胞介导的炎症反应与自噬功能异常的关联机制,总结二者在帕金森病发生发展中的作用及研究现状。结果 帕金森病是以多巴胺能神经元丢失与α-突触核蛋白异常聚集为核心病理特征的神经退行性疾病。NLRP3炎症小体过度激活与小胶质细胞自噬缺陷深度参与其病理进程。目前二者交互调控机制缺乏系统性整合。结论 NLRP3炎症小体过度激活、小胶质细胞自噬缺陷会协同加重多巴胺能神经元损伤,α-突触核蛋白病理扩散,从而加速疾病进展。活化小胶质细胞自噬可抑制NLRP3炎症小体的激活、发挥神经保护作用。二者动态互作调控帕金森病病程,靶向干预该调控轴可为该病临床防治提供新思路。小分子NLRP3抑制剂、天然自噬调节剂、脑靶向纳米制剂的联合制剂、细胞特异性前药可能是未来帕金森病新型治疗药物的研发方向。

关键词: 帕金森病, 靶向药物, NLRP3炎症小体, α-Synuclein, 自噬, 小胶质细胞

Abstract: Objective To elucidate the regulatory network linking microglial autophagy to NLRP3 inflammation so as to provide a reference for targeted interventions in Parkinson's disease. Methods The pathological mechanisms of Parkinson's disease, activation pathways of the NLRP3 inflammasome, and regulatory mechanisms of cellular autophagy were explored based on literature review. The underlying mechanisms linking microglia-mediated inflammatory responses to autophagy dysfunction were identified and their roles in the onset and progression of Parkinson's disease as well as the current research were summarized. Results Parkinson's disease is a neurodegenerative disorder characterized by the loss of dopaminergic neurons and the abnormal aggregation of α-synuclein. Overexpression of the NLRP3 inflammasome and defects in microglial autophagy are deeply involved in its pathological progression. Currently, there is a lack of systematic integration of the mechanisms of their mutual regulation. Conclusion Excessive activation of the NLRP3 inflammasome and defects in microglial autophagy synergistically exacerbate dopaminergic neuron damage and the pathological spread of α-synuclein, thereby accelerating disease progression. Conversely, activating microglial autophagy can inhibit NLRP3 inflammasome activation and exert neuroprotective effects. The dynamic interactions between these two processes regulate the course of Parkinson's disease, and targeted intervention in this regulatory axis may provide new insights into the clinical prevention and treatment of the disease. The combined formulations of small-molecule NLRP3 inhibitors, natural autophagy modulators, brain-targeted nanodrugs, and cell-specific prodrugs may promise a new sphere of research for the development of novel Parkinson's disease therapeutics.

Key words: Parkinson's Disease, Targeted Drugs, NLRP3 Inflammasome, α-Synuclein, Autophagy, Microglia

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