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- Title
MiR-124 Regulates Apoptosis and Autophagy Process in MPTP Model of Parkinson's Disease by Targeting to Bim.
- Authors
Wang, Huiqing; Ye, Yongyi; Zhu, Zhiyuan; Mo, Liqian; Lin, Chunnan; Wang, Qifu; Wang, Haoyuan; Gong, Xin; He, Xiaozheng; Lu, Guohui; Lu, Fengfei; Zhang, Shizhong
- Abstract
Parkinson's disease ( PD) is the most prevalent movement disorder characterized by selective loss of midbrain dopaminergic ( DA) neurons. MicroRNA-124 (mi R-124) is abundantly expressed in the DA neurons and its expression level decreases in the 1-methyl-4-pheny-1, 2, 3, 6-tetrahydropyridine ( MPTP) model of PD. However, whether the upregulation of miR-124 could attenuate neurodegeneration remains unknown. Here, we employed miR-124 agomir and miR-124 mimics to upregulate mi R-124 expression in MPTP-treated mice and MPP+-intoxicated SH- SY5Y cells, respectively. We found that loss of DA neurons and striatal dopamine in MPTP-treated mice was significantly reduced by upregulating mi R-124. In addition, we identified a target of mi R-124, Bim that mediated the neuroprotection of mi R-124. Indeed, treatment of mi R-124 agomir in MPTP-treated mice inhibited Bim expression, thus suppressing Bax translocation to mitochondria. Moreover, impaired autophagy process in MPTP-treated mice and MPP+-intoxicated SH- SY5Y cells characterized as autophagosomes ( AP) accumulation and lysosomal depletion were alleviated by the upregulation of miR-124. Taken together, these results indicate that upregulation of mi R-124 could regulate apoptosis and impaired autophagy process in the MPTP model of PD, thus reducing the loss of DA neurons.
- Subjects
PARKINSON'S disease; DOPAMINERGIC neurons; MOVEMENT disorders; NEURODEGENERATION; AUTOPHAGY; MICRORNA
- Publication
Brain Pathology, 2016, Vol 26, Issue 2, p167
- ISSN
1015-6305
- Publication type
Article
- DOI
10.1111/bpa.12267