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ORIGINAL RESEARCH article
Front. Neurosci.
Sec. Neurodegeneration
Volume 18 - 2024 |
doi: 10.3389/fnins.2024.1420507
This article is part of the Research Topic Neuroinflammation and Neurodegenerative Diseases View all 6 articles
α-Synuclein-mediated mitochondrial translocation of cofilin 1 leads to oxidative stress and cell apoptosis in PD
Provisionally accepted
Mingmin Yan
1
Qian Zhang
1*
Yu Chen
1*
Chenyi Zhu
1*
Dan Wang
1*
Jie Tan
1*
Bihua He
1*
Qin Li
1*
Zhentao Zhang
2
Xiaorong Deng
1*
Yue Wan
1*- 1 Hubei Provincial Third People's Hospital (Zhongshan Hospital), Wuhan, Hubei Province, China
- 2 Department of Neurology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China
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.
Keywords: α-Synuclein, Cofilin 1, Mitochondria, Oxidative Stress, Apoptosis, Parkinsion's disease
Received: 20 Apr 2024; Accepted: 23 Jul 2024.
Copyright: © 2024 Yan, Zhang, Chen, Zhu, Wang, Tan, He, Li, Zhang, Deng and Wan. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Qian Zhang, Hubei Provincial Third People's Hospital (Zhongshan Hospital), Wuhan, 430000, Hubei Province, China
Yu Chen, Hubei Provincial Third People's Hospital (Zhongshan Hospital), Wuhan, 430000, Hubei Province, China
Chenyi Zhu, Hubei Provincial Third People's Hospital (Zhongshan Hospital), Wuhan, 430000, Hubei Province, China
Dan Wang, Hubei Provincial Third People's Hospital (Zhongshan Hospital), Wuhan, 430000, Hubei Province, China
Jie Tan, Hubei Provincial Third People's Hospital (Zhongshan Hospital), Wuhan, 430000, Hubei Province, China
Bihua He, Hubei Provincial Third People's Hospital (Zhongshan Hospital), Wuhan, 430000, Hubei Province, China
Qin Li, Hubei Provincial Third People's Hospital (Zhongshan Hospital), Wuhan, 430000, Hubei Province, China
Xiaorong Deng, Hubei Provincial Third People's Hospital (Zhongshan Hospital), Wuhan, 430000, Hubei Province, China
Yue Wan, Hubei Provincial Third People's Hospital (Zhongshan Hospital), Wuhan, 430000, Hubei Province, China
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