AUTHOR=Yan Mingmin , Zhang Qian , Chen Yu , Zhu Chenyi , Wang Dan , Tan Jie , He Bihua , Li Qin , Deng Xiaorong , Wan Yue 

TITLE=α-Synuclein-mediated mitochondrial translocation of cofilin-1 leads to oxidative stress and cell apoptosis in PD

JOURNAL=Frontiers in Neuroscience

VOLUME=Volume 18 - 2024

YEAR=2024

URL=https://www.frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2024.1420507

DOI=10.3389/fnins.2024.1420507

ISSN=1662-453X

ABSTRACT=Parkinson’s disease (PD) is characterized by the accumulation of misfolded α-synuclein protein and loss of dopaminergic neurons in the substantia nigra. Abnormal α-synuclein aggregates form toxic Lewy bodies and finally induce neuronal injury. Mitochondrial dysfunction was reported to be involved in the neurotoxicity of α-synuclein aggregates in PD. However, the specific mechanism by which abnormal α-synuclein aggregates exert mitochondrial disorders remains poorly defined. Previously we found that cofilin 1, a member of the actin-binding protein, regulates α-synuclein pathogenicity by promoting its aggregation and spreading in vitro and in vivo. Here we further investigated the effect of cofilin 1 on α-synuclein induced mitochondrial damage. We discovered that α-synuclein aggregates accelerate the translocation of cofilin 1 to mitochondria, then promote its combination with mitochondrial outer membrane receptor Tom 20, and ultimately activate the oxidative damage and apoptosis pathway in mitochondria. All these results demonstrate the important regulatory role of cofilin 1 in the mitochondrial neurotoxicity of pathological α-synuclein during the progression of PD.