MiR-124 Regulates Apoptosis and Autophagy Process in MPTP Model of Parkinson's Disease by Targeting to Bim
MiR-124 Regulates Apoptosis and Autophagy Process in MPTP Model of Parkinson's Disease by Targeting to Bim
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MiR-124 通过靶向 Bim 调节帕金森病 MPTP 模型中的细胞凋亡和自噬过程
DOI：
10.1111/bpa.12267
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发表时间：
2016-03-01
期刊：
影响因子：
6.4
通讯作者：
Zhang, Shizhong
中科院分区：
文献类型：
--
作者：
Wang, Huiqing;Ye, Yongyi;Zhang, Shizhong
帕金森病（Parkinson's disease，PD）是一种以中脑多巴胺能（dopaminergic，DA）神经元选择性缺失为特征的运动障碍。MicroRNA-124（miR-124）在DA神经元中大量表达，在1-甲基-4-苯基-1，2，3，6-四氢吡啶（MPTP）模型中表达水平降低。然而，miR-124的上调是否可以减轻神经变性仍然未知。在这里，我们分别使用miR-124 agomir和miR-124模拟物上调MPTP处理的小鼠和MPP+中毒的SH-SY 5 Y细胞中的miR-124表达。我们发现，通过上调miR-124，MPTP处理小鼠中DA神经元和纹状体多巴胺的损失显著减少。此外，我们确定了miR-124的靶点Bim介导miR-124的神经保护作用。事实上，在MPTP处理的小鼠中，miR-124 agomir的处理抑制了Bim的表达，从而抑制了Bax向线粒体的移位。此外，MPTP处理的小鼠和MPP+中毒的SH-SY 5 Y细胞中受损的自噬过程的特征在于自噬体（AP）积累和溶酶体消耗通过miR-124的上调而减轻。综上所述，这些结果表明，在PD的MPTP模型中，miR-124的上调可以调节细胞凋亡和受损的自噬过程，从而减少DA神经元的损失。
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.