Mitochondrial morphogenesis, distribution, and Parkinson disease: insights from PINK1.
Mitochondrial morphogenesis, distribution, and Parkinson disease: insights from PINK1.
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DOI：
10.1097/nen.0b013e3181b2048c
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发表时间：
2009-09
影响因子：
3.2
通讯作者：
Lu B
中科院分区：
文献类型：
--
作者：
Yang Y;Lu B
帕金森病（PD）的病因被认为是环境因素、内在细胞代谢特性和易感基因的复杂组合。在PD中开发神经保护疗法的主要障碍包括关于神经元功能障碍的确切原因和靶向的不确定性。在过去的10年中，与遗传形式的PD相关的孟德尔基因的发现彻底改变了对导致神经元功能障碍的细胞通路的理解。PD发病机制的共同主题开始出现，线粒体功能障碍处于中心阶段。在这篇综述中，我们总结了我们的知识，PD的发病机制，重新访问线粒体生物学的一些方面，并讨论了从研究的Pink1，一个家族性PD相关基因的见解。我们认为，线粒体形态发生和分布可能是PD和其他神经退行性疾病研究的一种新的和潜在的共同范式，并且这种线粒体过程的调节可能被证明是PD的一种有价值的治疗途径。
The etiology of Parkinson disease (PD) has been assumed to be a complex combination of environmental factors, intrinsic cellular metabolic properties, and susceptible genetic alleles. The primary obstacles to the development of a neuroprotective therapy in PD include uncertainties with regard to the precise cause(s) of neuronal dysfunction and what to target. The discoveries of Mendelian genes associated with inherited forms of PD in the last 10 years have revolutionized the understanding of the cellular pathways leading to neuronal dysfunction. Common themes of the pathogenesis of PD are beginning to emerge with mitochondrial dysfunction at the center stage. In this review, we summarize our knowledge of the pathogenesis of PD, revisit some aspects of mitochondrial biology, and discuss the insights from the study of Pink1, a familial PD-associated gene. We propose that mitochondrial morphogenesis and distribution might be a novel and potential common paradigm for PD and other neurodegenerative disease research and that modulation of such mitochondrial processes may prove to be a valuable therapeutic avenue for PD.