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Brain Pathol. 2016 Mar;26(2):167-76. doi: 10.1111/bpa.12267. Epub 2015 Jun 11.

MiR-124 Regulates Apoptosis and Autophagy Process in MPTP Model of Parkinson's Disease by Targeting to Bim.

Wang H1,2, Ye Y1,2, Zhu Z1,2, Mo L3, Lin C1,2, Wang Q1,2, Wang H1,2, Gong X2,4, He X1,2, Lu G5, Lu F1,2, Zhang S1,2.

Author information

1
Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
2
The National Key Clinic Specialty, The Neurosurgery Institute of Guangdong Province, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, Southern Medical University, Guangzhou, China.
3
Department of Pharmacy, Nanfang Hospital, Southern Medical University, Guangzhou, China.
4
Department of Neurosurgery, Hunan Provincial People's Hospital, Changsha, China.
5
Department of Neurosurgery, the First Affiliated Hospital of Nanchang University, Nanchang, China.

Abstract

Parkinson's disease (PD) is the most prevalent movement disorder characterized by selective loss of midbrain dopaminergic (DA) neurons. MicroRNA-124 (miR-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 miR-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 miR-124. In addition, we identified a target of miR-124, Bim that mediated the neuroprotection of miR-124. Indeed, treatment of miR-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 miR-124 could regulate apoptosis and impaired autophagy process in the MPTP model of PD, thus reducing the loss of DA neurons.

KEYWORDS:

Bax; Bim; Parkinson's disease; apoptosis; autophagy; miR-124

PMID:
25976060
DOI:
10.1111/bpa.12267
[Indexed for MEDLINE]

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