Mitophagy and cGAS-STING crosstalk in neuroinflammation

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外文摘要：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 criti-cally evaluate the literature demonstrating how dysfunctional mitophagy leads to neuroinflammatory con-ditions,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 neurodegenera-tive 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 syn-thesis enhances our understanding of the cellular and molecular foundations of neuroinflammation and opens new therapeutic avenues for neurodegenerative disease research.

外文关键词：

NeuroinflammationMitophagycGAS-STINGInnate immunityMitochondrial DNACrosstalkTherapeutic avenuesNeurodegenerative diseases

作者：

Xiaogang Zhou、Jing Wang、Lu Yu、Gan Qiao、Dalian Qin、Betty Yuen-Kwan Law、Fang Ren、Jianming Wu、Anguo Wu

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作者单位：

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

Chongqing Key Laboratory of Sichuan-Chongqing Co-construction for Diagnosis and Treatment of Infectious Diseases Integrated Traditional Chinese and Western Medicine,Chongqing Traditional Chinese Medicine Hospital,Chongqing 400021,China

基金：

Natural Science Foundation of ChinaDepartment of Science and Technology of Sichuan Province,ChinaDepartment of Science and Technology of Sichuan Province,ChinaDepartment of Science and Technology of Sichuan Province,ChinaMacao Science and Technology Development Fund of Macao SAR,ChinaMacao Science and Technology Development Fund of Macao SAR,ChinaSouthwest Medical University,ChinaSouthwest Medical University,ChinaSouthwest Medical University,ChinaCentral Government Funds of Guiding Local Scientific and Technological Development,ChinaLuzhou Science and Technology Project,China

项目编号：

819038292022YFS06202024YFHZ036122ZDYF3784SKL-QRCMMUST-2020-2022MUST-SKL-2021-0052021ZKZD0152021ZKZD0182021ZKMS04623ZYZYTS02112022-SYF-73

出版年：

2024

DOI：

10.1016/j.apsb.2024.05.012

药学学报(英文版)

CSTPCD

ISSN：

年,卷(期)：2024.14(8)