Wu Xian, Wan Teng, Gao Xiaoyu, Fu Mingyuan, Duan Yunfeng, Shen Xiangru, Guo Weiming
The First Affiliated Hospital of Hunan College of Traditional Chinese Medicine, Hunan Province Directly Affiliated TCM Hospital, Zhuzhou, China.
Huazhong University of Science and Technology Union Shenzhen Hospital, The 6th Affiliated Hospital of Shenzhen University Health Science Center, Shenzhen, China.
Front Neurosci. 2022 Jul 22;16:922331. doi: 10.3389/fnins.2022.922331. eCollection 2022.
In addition to its profound implications in the fight against cancer, pyroptosis have important role in the regulation of neuronal injury. Microglia are not only central members of the immune regulation of the central nervous system (CNS), but are also involved in the development and homeostatic maintenance of the nervous system. Under various pathological overstimulation, microglia pyroptosis contributes to the massive release of intracellular inflammatory mediators leading to neuroinflammation and ultimately to neuronal damages. In addition, microglia pyroptosis lead to further neurological damage by decreasing the ability to cleanse harmful substances. The pathogenic roles of microglia in a variety of CNS diseases such as neurodegenerative diseases, stroke, multiple sclerosis and depression, and many other neurological disorders have been gradually unveiled. In the context of different neurological disorders, inhibition of microglia pyroptosis by targeting NOD-like receptor family pyrin domain containing (NLRP) 3, caspase-1 and gasdermins (GSDMs) by various chemical agents as well as natural products significantly improve the symptoms or outcome in animal models. This study will provide new ideas for immunomodulatory treatment of CNS diseases.
除了在抗癌斗争中具有深远意义外，细胞焦亡在神经元损伤的调节中也发挥着重要作用。小胶质细胞不仅是中枢神经系统（CNS）免疫调节的核心成员，还参与神经系统的发育和稳态维持。在各种病理性过度刺激下，小胶质细胞焦亡会导致细胞内炎症介质大量释放，引发神经炎症并最终导致神经元损伤。此外，小胶质细胞焦亡会降低清除有害物质的能力，从而进一步导致神经损伤。小胶质细胞在多种中枢神经系统疾病（如神经退行性疾病、中风、多发性硬化症和抑郁症）以及许多其他神经疾病中的致病作用已逐渐被揭示。在不同神经疾病的背景下，通过各种化学试剂以及天然产物靶向含核苷酸结合寡聚化结构域样受体家族pyrin结构域（NLRP）3、半胱天冬酶 -1和gasdermin（GSDM）来抑制小胶质细胞焦亡，可显著改善动物模型的症状或预后。本研究将为中枢神经系统疾病的免疫调节治疗提供新思路。
