Zhou Xiaogang, Wang Jing, Yu Lu, Qiao Gan, Qin Dalian, Yuen-Kwan Law Betty, Ren Fang, Wu Jianming, Wu Anguo
Sichuan Key Medical Laboratory of New Drug Discovery and Drugability Evaluation, Luzhou Key Laboratory of Activity Screening and Druggability Evaluation for Chinese Materia Medica, Key Laboratory of Medical Electrophysiology of Ministry of Education, School of Pharmacy, Southwest Medical University, Luzhou 646000, China.
State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau SAR 999078, China.
Acta Pharm Sin B. 2024 Aug;14(8):3327-3361. doi: 10.1016/j.apsb.2024.05.012. Epub 2024 May 13.
Mitophagy, essential for mitochondrial health, selectively degrades damaged mitochondria. It is intricately linked to the cGAS-STING pathway, which is crucial for innate immunity. This pathway responds to mitochondrial DNA and is associated with cellular stress response. Our review explores the molecular details and regulatory mechanisms of mitophagy and the cGAS-STING pathway. We critically evaluate the literature demonstrating how dysfunctional mitophagy leads to neuroinflammatory conditions, primarily through the accumulation of damaged mitochondria, which activates the cGAS-STING pathway. This activation prompts the production of pro-inflammatory cytokines, exacerbating neuroinflammation. This review emphasizes the interaction between mitophagy and the cGAS-STING pathways. Effective mitophagy may suppress the cGAS-STING pathway, offering protection against neuroinflammation. Conversely, impaired mitophagy may activate the cGAS-STING pathway, leading to chronic neuroinflammation. Additionally, we explored how this interaction influences neurodegenerative disorders, suggesting a common mechanism underlying these diseases. In conclusion, there is a need for additional targeted research to unravel the complexities of mitophagy-cGAS-STING interactions and their role in neurodegeneration. This review highlights potential therapies targeting these pathways, potentially leading to new treatments for neuroinflammatory and neurodegenerative conditions. This synthesis enhances our understanding of the cellular and molecular foundations of neuroinflammation and opens new therapeutic avenues for neurodegenerative disease research.
线粒体自噬对线粒体健康至关重要，它能选择性地降解受损的线粒体。它与cGAS-STING通路密切相关，而该通路对先天免疫至关重要。这条通路对线粒体DNA做出反应，并与细胞应激反应相关。我们的综述探讨了线粒体自噬和cGAS-STING通路的分子细节和调控机制。我们批判性地评估了文献，这些文献表明功能失调的线粒体自噬如何主要通过受损线粒体的积累激活cGAS-STING通路，从而导致神经炎症状态。这种激活促使促炎细胞因子的产生，加剧神经炎症。本综述强调了线粒体自噬与cGAS-STING通路之间的相互作用。有效的线粒体自噬可能会抑制cGAS-STING通路，提供针对神经炎症的保护。相反，线粒体自噬受损可能会激活cGAS-STING通路，导致慢性神经炎症。此外，我们探讨了这种相互作用如何影响神经退行性疾病，提示这些疾病存在共同的机制。总之，需要更多有针对性的研究来揭示线粒体自噬-cGAS-STING相互作用的复杂性及其在神经退行性变中的作用。本综述强调了针对这些通路的潜在疗法，可能会为神经炎症和神经退行性疾病带来新的治疗方法。这种综合分析增强了我们对神经炎症的细胞和分子基础的理解，并为神经退行性疾病研究开辟了新的治疗途径。
