Mitochondrial dynamics and mitophagy in the 6-hydroxydopamine preclinical model of Parkinson's disease.
Mitochondrial dynamics and mitophagy in the 6-hydroxydopamine preclinical model of Parkinson's disease.
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DOI：
10.1155/2012/131058
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发表时间：
2012
期刊：
影响因子：
--
通讯作者：
Jordán Bueso J
中科院分区：
文献类型：
--
作者：
Galindo MF;Solesio ME;Atienzar-Aroca S;Zamora MJ;Jordán Bueso J
我们讨论了线粒体动力学和自噬在6-羟多巴胺诱导的帕金森病模型的参与。动态线粒体过程如融合、分裂和线粒体自噬的调节已被证明是控制细胞命运的重要机制。线粒体动力学的不平衡可能导致家族性和散发性神经退行性疾病，包括帕金森病。我们特别注意第二信使的作用，作为活性氧的作用和线粒体作为细胞死亡的总部。分子信号通路的作用，例如，发动蛋白相关蛋白1（Drp 1）的参与，也将得到解决。此外，有证据表明小分子线粒体分裂抑制剂在帕金森病中的治疗潜力。例如，通过用线粒体分裂抑制剂-1治疗，药物抑制Drp 1导致线粒体分裂的消除和自噬细胞数量的减少。破译由6-OHDA触发的线粒体自噬的信号级联，以及决定这种反应选择性的机制，将有助于更好地理解这一过程，并可能对帕金森病的人类治疗策略产生影响。
We discuss the participation of mitochondrial dynamics and autophagy in the 6-hydroxidopamine-induced Parkinson's disease model. The regulation of dynamic mitochondrial processes such as fusion, fission, and mitophagy has been shown to be an important mechanism controlling cellular fate. An imbalance in mitochondrial dynamics may contribute to both familial and sporadic neurodegenerative diseases including Parkinson's disease. With special attention we address the role of second messengers as the role of reactive oxygen species and the mitochondria as the headquarters of cell death. The role of molecular signaling pathways, for instance, the participation of Dynamin-related protein 1(Drp1), will also be addressed. Furthermore evidence demonstrates the therapeutic potential of small-molecule inhibitors of mitochondrial division in Parkinson's disease. For instance, pharmacological inhibition of Drp1, through treatment with the mitochondrial division inhibitor-1, results in the abrogation of mitochondrial fission and in a decrease of the number of autophagic cells. Deciphering the signaling cascades that underlie mitophagy triggered by 6-OHDA, as well as the mechanisms that determine the selectivity of this response, will help to better understand this process and may have impact on human treatment strategies of Parkinson's disease.
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