期刊
MOLECULAR NEUROBIOLOGY
卷 59, 期 2, 页码 1333-1344出版社
SPRINGER
DOI: 10.1007/s12035-021-02670-w
关键词
Parkinson's disease; Biomarker; PP2A; CIP2A; Alpha-synuclein
资金
- National Key R&D Program of China [2017YFC1310200, 2016YFC1306000]
- National Natural Science Foundation of China [81974201, 81671260]
This study identified and validated cancerous inhibitor of PP2A (CIP2A) as a potential diagnostic biomarker for Parkinson's disease (PD). The results showed that plasma CIP2A concentrations were significantly lower in PD patients compared to controls, and CIP2A played a role in PD-related pathogenesis in cellular and mouse models. This suggests that CIP2A could be a novel biomarker for PD.
Parkinson's disease (PD) is an incurable neurodegenerative disease characterized by aggregation of pathological alpha-synuclein (alpha-syn) and loss of dopaminergic neuron in the substantia nigra. Inhibition of phosphorylation of the alpha-syn has been shown to mediate alleviation of PD-related pathology. Protein phosphatase 2A (PP2A), an important serine/threonine phosphatase, plays an essential role in catalyzing dephosphorylation of the alpha-syn. Here, we identified and validated cancerous inhibitor of PP2A (CIP2A), as a potential diagnostic biomarker for PD. Our data showed that plasma CIP2A concentrations in PD patients were significantly lower compared to age- and sex-matched controls, 1.721 (1.435-2.428) ng/ml vs 3.051(2.36-5.475) ng/ml, p < 0.0001. The area under the curve of the plasma CIP2A in distinguishing PD from the age- and sex-matched controls was 0.776. In addition, we evaluated the role of CIP2A in PD-related pathogenesis in PD cellular and MPTP-induced mouse model. The results demonstrated that CIP2A is upregulated in PD cellular and MPTP-induced mouse models. Besides, suppression of the CIP2A expression alleviates rotenone induced aggregation of the alpha-syn as well as phosphorylation of the alpha-syn in SH-SY5Y cells, which is associated with increased PP2A activity. Taken together, our data demonstrated that CIP2A plays an essential role in the mechanisms related to PD development and might be a novel PD biomarker.
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