Loss of Drosha underlies dopaminergic neuron toxicity in models of Parkinson's disease.
Loss of Drosha underlies dopaminergic neuron toxicity in models of Parkinson's disease.
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DOI：
10.1038/s41419-018-0716-5
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发表时间：
2018-06-07
影响因子：
9
通讯作者：
Yang Q
中科院分区：
文献类型：
--
作者：
Wang R;Lu F;Zhu G;Feng D;Nie T;Tao K;Yang S;Lei J;Huang L;Mao Z;Yang Q
miRNAs是一组功能强大的基因表达调控因子，在生理和病理条件下参与多种细胞过程。新出现的证据表明，Drosha控制着典型miRNA生物发生的初始步骤，参与调节几种疾病模型中的细胞存活和死亡。然而，Drosha在帕金森病（PD）中的作用尚未得到很好的确立。在这里，我们表明，在6-OHDA诱导的PD细胞和动物模型中，Drosha的水平降低。6-OHDA诱导Drosha的p38 MAPK依赖性磷酸化。这引发了Drosha的退化。提高Drosha的水平可以保护PD小鼠多巴胺能神经元免受6-OHDA诱导的毒性，并减轻PD小鼠的运动障碍。这些研究结果表明，Drosha在DA神经元的存活中起着关键作用，并表明应激诱导的Drosha不稳定可能是PD病理过程的一部分。
MiRNAs, a group of powerful modulator of gene expression, participate in multiple cellular processes under physiological and pathological conditions. Emerging evidence shows that Drosha, which controls the initial step in canonical miRNA biogenesis, is involved in modulating cell survival and death in models of several diseases. However, the role of Drosha in Parkinson’s disease (PD) has not been well established. Here, we show that the level of Drosha decreases in 6-OHDA-induced cellular and animal models of PD. 6-OHDA induced a p38 MAPK-dependent phosphorylation of Drosha. This triggered Drosha degradation. Enhancing the level of Drosha protected the dopaminergic (DA) neurons from 6-OHDA-induced toxicity in both in vitro and in vivo models of PD and alleviated the motor deficits of PD mice. These findings reveal that Drosha plays a critical role in the survival of DA neurons and suggest that stress-induced destabilization of Drosha may be part of the pathological process in PD.
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影响因子：
13.5
作者：
Junn, Eunsung;Mouradian, M. Maral
通讯作者：
Mouradian, M. Maral
通过基础神经节电路的光遗传控制对帕金森运动行为的调节。
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64.8
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64.8
作者：
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