Open AccessMiR ‐124 Regulates Apoptosis and Autophagy Process in MPTP Model of P arkinson's Disease by Targeting to B im
Author(s) -
Wang Huiqing,
Ye Yongyi,
Zhu Zhiyuan,
Mo Liqian,
Lin Chunnan,
Wang Qifu,
Wang Haoyuan,
Gong Xin,
He Xiaozheng,
Lu Guohui,
Lu Fengfei,
Zhang Shizhong
Publication year - 2016
Publication title -
brain pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.986
H-Index - 132
eISSN - 1750-3639
pISSN - 1015-6305
DOI - 10.1111/bpa.12267
Subject(s) - mptp , downregulation and upregulation , autophagy , neuroprotection , neurodegeneration , chemistry , apoptosis , dopaminergic , microbiology and biotechnology , pharmacology , biology , endocrinology , medicine , dopamine , biochemistry , disease , gene
P arkinson'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, B im that mediated the neuroprotection of mi R ‐124. Indeed, treatment of mi R ‐124 agomir in MPTP ‐treated mice inhibited B im expression, thus suppressing B ax 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.