Mechanism of alpha-synuclein in mitochondrial damage induced by Parkinson's disease

Wang Jingying; Ren Binbin; Ma Suna; Yang Yueyue; Wu Song; Guan Mengya

doi:10.12307/2025.626

Abstract：BACKGROUND:Currently,the pathogenesis of Parkinson's disease is not clear.Relevant studies have shown that α-synuclein and mitochondria are closely related to the pathogenesis of Parkinson's disease.It mainly involves oxidative stress,mitochondrial complex damage,calcium homeostasis,mitochondrial dynamics and mitochondrial quality control. OBJECTIVE:To review the association between α-synuclein and mitochondrial damage in Parkinson's disease. METHODS:The first author searched more than 50 documents from CNKI and WanFang databases from 2010 to 2024 using the keywords of"Parkinson's disease,mitochondrial damage and mechanism,α-synuclein"in Chinese as well as more than 750 documents from PubMed between 2010 and 2024 using the keywords of"Parkinson's disease,alpha-synuclein,mitochondria,oxidative stress,calcium homeostasis,mitophagy,mitochondrial dynamics,mitochondrial protein introduction"in English.Finally,70 documents were included for review. RESULTS AND CONCLUSION:Recent studies have confirmed the important role of mitochondrial dysfunction in the pathophysiology of Parkinson's disease,and the interaction between α-synuclein and mitochondria is a particularly significant factor in the pathogenesis of Parkinson's disease.The cascade of events that begin with naturally unfolded α-synuclein and eventually form mature fibril is collectively known as α-synuclein aggregation.The toxicity of aggregation accumulates in dopaminergic neurons and then disrupts mitochondrial function,thereby triggering Parkinson's disease.Therefore,the underlying mechanism of this bidirectional relationship between α-synuclein and mitochondrial dysfunction may provide new insights into the pathophysiology of Parkinson's disease.