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MicroRNA-10a Inhibits A30P α-synuclein Aggregation and Toxicity by Targeting Proapoptotic Protein BCL2L11

MicroRNA-10a Inhibits A30P α-synuclein Aggregation and Toxicity by Targeting Proapoptotic Protein BCL2L11

Huimin Liang, Bingqian Ding, Junhui Liang, Xiaoyan Shi, Xin Jiang, Yang Gao

Int J Clin Exp Pathol. 2018 Feb 1;11(2):624-633.

PMID: 31938148

Abstract:

Parkinson's disease (PD) is the second most common neurodegenerative disorder around the world, and is characterized by progressive loss of nigrostriatal dopaminergic neurons. Certain microRNAs (miRNAs) are aberrantly expressed in the post-mortem brain tissues of patients with PD and in vivo PD model mice. However, the role of brain-enriched miRNA (miR)-10a in PD has not been studied. To investigate the regulatory role of miR-10a on α-synuclein (α-syn) in the pathology of PD, the present study aimed to examine whether upregulation of miR-10a attenuated A30P α-syn mutant aggregation and cellular toxicity. miRNA expression analysis by reverse transcription-quantitative polymerase chain reaction demonstrated that miR-10a expression was decreased in the midbrain of A30P α-syn transgenic mice and in SH-SY5Y human neuroblastoma cells transfected with A30P α-syn. In addition, miR-10a mimics were used to upregulate miR-10a expression. It was revealed that the upregulation of miR-10a suppressed α-syn intracellular accumulation and toxicity in α-syn-overexpressing SH-SY5Y cells. In addition, miR-10a overexpression resulted in a reversal of the A30P α-syn-induced upregulation of proapoptotic protein Bcl-2-associated X protein and cleaved caspase-3 expression and downregulation of antiapoptotic protein B-cell lymphoma-2 (BCL2) expression. A luciferase reporter assay demonstrated that BCL2-like 11 (BCL2L11), an apoptosis inducer, was a novel target gene of miR-10a. A30P α-syn aggregation and toxicity were alleviated by knocking down endogenous BCL2L11 in SH-SY5Y cells using a small interfering RNA specific for BCL2L11. In conclusion, these results demonstrate that miR-10a may serve a functional role in α-syn-induced neuronal pathology by inhibiting expression of BCL2L11 and that upregulation of miR-10a expression may be a useful therapeutic strategy for the treatment of PD.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
IAR4248205	α-Synuclein A30P human			Price

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