Neuroreport. 2021 Oct 13;32(15):1263-1268.doi: 10.1097/WNR.0000000000001721.

Annexin A2 degradation contributes to dopaminergic cell apoptosis via regulating p53 in neurodegenerative conditions



  • 1 Department of Neurology, Affiliated Hospital of Beihua University, Jilin, China.
  • 2 Department of Health Policy and Management, Emory University Rollins School of Public Health, Georgia, USA.
  • 3 Department of Rehabilitation, Shan Dong Rehabilitation Hospital, JiNang.
  • 4 Department of General Practic, Shanghai Songjiang District Central Hospital, Shanghai, P.R.China.


Background: P53 overexpression has been shown to involve in mitochondria-mediated dapaminergic neuron cell death in Parkinson’s disease. However, the exactly molecular mechanisms responsible for the p53-dependent intrinsic cell death in neurodegenerative conditions remain unclearly. Annexin A2 is a multifunctional protein that negatively regulates p53 expression. The purpose of this study was to explore the mechanism of p53 dependent dopaminergic cell death and implication of Annexin A2 in cellular apoptosis in 1-methyl-4-phenylpyridinium (MPP+)-induced PC12 cells.

Methods: The cell viability of neural PC12 cells was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltet-razolium bromide assay. Flow cytometry was used to evaluate the apoptosis and mitochondrial transmembrane potential of neural PC12 cells. The expression of p53 and Annexin A2 was analyzed by western blot assay.

Results: The present study showed that the exposure of PC12 cells to neurotoxin MPP+ increased the expression levels of p53 and the discharge of mitochondrial transmembrane potential. Notably, Annexin A2 degradation was also observed in this cellular model of Parkinson’s disease, in a time and dose-dependent manner. This expressing change of Annexin A2 was in direct proportion to the loss of cell viability of PC12 cells, and this expression pattern was in inverse proportion to p53 levels in this cellular model of Parkinson’s disease.

Conclusion: These results indicated that Annexin A2 degradation plays a crucial role the degeneration of dapaminergic cells of Parkinson’s disease, and Annexin A2 downregulation-mediated the cell death is closely associated with mitochondrial dysfunction via p53-dependent pathway; thus provide a novel therapeutic target for Parkinson’s disease treatment.