ADP/ATP translocase 1 protects against an α-synuclein-associated neuronal cell damage in Parkinson’s disease model

Cell & Bioscience

Wenli Zhang¹  Xuefei Xu¹  Minghua Qi¹  Wenyong Ding¹  Li Ma²  Yingfei Chen³ 

[1] Biochemistry and Molecular Biology Department of College of Basic Medical Sciences, Dalian Medical University, 116044, Dalian, China;Department of Epidemiology, Dalian Medical University, 116044, Dalian, China;Grade 2020, Capital Medical University, 100069, Beijing, China;

关键词: ADP/ATP translocase 1;    Parkinson’s disease;    PD;    ANT1;    α-synuclein;   

DOI  :  10.1186/s13578-021-00645-x

来源: Springer

【 摘 要 】

BackgroundADP/ATP translocase 1 (ANT1) is involved in the exchange of cytosolic ADP and mitochondrial ATP, and its defection plays an important role in mitochondrial pathogenesis. To reveal an etiological implication of ANT1 for Parkinson’s disease (PD), a neurodegenerative disorder, a mouse model treated with 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine and neuroblastoma cell model induced by 1-methyl-4-pehny1-pyridine were utilized in this study.ResultsThe tissue-specific abundance in ANT1 in mouse brains was accessed using the analysis of Western blot and immunohistochemistry. Down-regulated soluble ANT1 was found to be correlated with PD, and ANT1 was associated with PD pathogenesis via forming protein aggregates with α-synuclein. This finding was confirmed at cellular level using neuroblastoma cell models. ANT1 supplement in neuronal cells revealed the protective roles of ANT1 against cytotoxicity caused by MPP+. Protein interaction assay, coupled with the analysis of LC-MS/MS, silver-stained SDS-PAGE and Western blot against anti-ANT1 antibody respectively, illustrated the interaction of ANT1 with α-synuclein using the expressed α-synuclein as a bite. Additionally, a significant increasing ROSs was detected in the MPP+-treated cells.ConclusionsThis study indicated that ANT1 was a potentially causative factor of PD, and led to neuropathogenic injury via promoting the formation of protein aggregates with α-synuclein. This investigation potentially promotes an innovative understanding of ANT1 on the etiology of PD and provides valuable information on developing potential drug targets in PD treatment or reliable biomarkers in PD prognostication.

【 授权许可】

CC BY