Advances in the Understanding of Mitochondrial Inflammatory Regulation in the Pathogenesis of Alzheimer’s Disease

Ren-Zhen Zhang,1,* Li Li,1,* Cui Ma,1 Ting-Ting Dou,1 Yu-Ting Wei,1 Xing-Ke Yan1,2 1School of Acupuncture-Moxibustion and Tuina, Gansu University of Traditional Chinese Medicine, Lanzhou, People’s Republic of China; 2Gansu Provincial Traditional Chinese Medicine Research Center, Lanzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xing-Ke Yan, Acupuncture and moxibustion and Massage College of Gansu University of Traditional Chinese Medicine, 35 Dingxi East Road, Lanzhou, People’s Republic of China, Email [email protected]: Mitochondria, beyond serving as the powerhouse of the cell, play a pivotal role in the regulation of inflammatory responses. Mitochondrial dysfunction-induced immune activation and chronic inflammation are deeply implicated in the pathogenesis of Alzheimer’s disease (AD), influencing its onset and progression through multiple inflammatory pathways. This review summarizes the involvement of several mitochondrial-related mechanisms in AD, including the release of mitochondrial DNA (mtDNA), signal transduction via mitochondrial antiviral-signaling protein (MAVS), the accumulation of mitochondrial damage-associated molecular patterns (DAMPs), the regulation of mitophagy, and the activation of the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway. These insights aim to shed new light on mitochondrial inflammation as a regulatory mechanism in AD and to explore its potential as a therapeutic target.Keywords: Alzheimer’s disease, mitochondrion, neuroinflammation, inflammatory mechanism, review