Center for Neuroscience and Cell Biology (CNC), University of Coimbra, Largo Marquês de Pombal, 3004-517 Coimbra, Portugal.
Parkinsons Dis. 2011 Feb 20;2011:767230. doi: 10.4061/2011/767230.
Understanding the molecular basis of Parkinson's disease (PD) has proven to be a major challenge in the field of neurodegenerative diseases. Although several hypotheses have been proposed to explain the molecular mechanisms underlying the pathogenesis of PD, a growing body of evidence has highlighted the role of mitochondrial dysfunction and the disruption of the mechanisms of mitochondrial dynamics in PD and other parkinsonian disorders. In this paper, we comment on the recent advances in how changes in the mitochondrial function and mitochondrial dynamics (fusion/fission, transport, and clearance) contribute to neurodegeneration, specifically focusing on PD. We also evaluate the current controversies in those issues and discuss the role of fusion/fission dynamics in the mitochondrial lifecycle and maintenance. We propose that cellular demise and neurodegeneration in PD are due to the interplay between mitochondrial dysfunction, mitochondrial trafficking disruption, and impaired autophagic clearance.
了解帕金森病 (PD) 的分子基础被证明是神经退行性疾病领域的一个主要挑战。尽管已经提出了几个假说来解释 PD 发病机制的分子机制，但越来越多的证据强调了线粒体功能障碍和线粒体动力学机制破坏在 PD 和其他帕金森氏症中的作用。在本文中，我们评论了线粒体功能和线粒体动力学（融合/裂变、运输和清除）变化如何导致神经退行性变的最新进展，特别是针对 PD。我们还评估了这些问题的当前争议，并讨论了融合/裂变动力学在线粒体生命周期和维持中的作用。我们提出，PD 中的细胞死亡和神经退行性变是由于线粒体功能障碍、线粒体运输中断和自噬清除受损之间的相互作用所致。
