Diabetes and Obesity Program, Garvan Institute of Medical Research, Sydney, NSW 2010, Australia.
Parkinsons Dis. 2012;2012:829207. doi: 10.1155/2012/829207. Epub 2012 Jun 10.
Parkinson's Disease (PD) is a complex, chronic, progressive, and debilitating neurodegenerative disorder. Neither a cure nor effective long-term therapy exist and the lack of knowledge of the molecular mechanisms responsible for PD development is a major impediment to therapeutic advances. The protein αSynuclein is a central component in PD pathogenesis yet its cellular targets and mechanism of toxicity remains unknown. Mitochondrial dysfunction is also a common theme in PD patients and this review explores the strong possibility that αSynuclein and mitochondrial dysfunction have an inter-relationship responsible for underlying the disease pathology. Amplifying cycles of mitochondrial dysfunction and αSynuclein toxicity can be envisaged, with either being the disease-initiating factor yet acting together during disease progression. Multiple potential mechanisms exist in which mitochondrial dysfunction and αSynuclein could interact to exacerbate their neurodegenerative properties. Candidates discussed within this review include autophagy, mitophagy, mitochondrial dynamics/fusion/fission, oxidative stress and reactive oxygen species, endoplasmic reticulum stress, calcium, nitrosative stress and αSynuclein Oligomerization.
帕金森病（PD）是一种复杂的、慢性的、进行性的、使人衰弱的神经退行性疾病。既没有治愈方法，也没有有效的长期治疗方法，而对导致 PD 发展的分子机制缺乏了解是治疗进展的主要障碍。α-突触核蛋白是 PD 发病机制中的一个核心组成部分，但它的细胞靶标和毒性机制仍然未知。线粒体功能障碍也是 PD 患者的一个常见主题，本综述探讨了 α-突触核蛋白和线粒体功能障碍之间存在相互关系的可能性，这种相互关系可能是导致疾病病理的基础。可以设想线粒体功能障碍和 α-突触核蛋白毒性的放大循环，两者都可能是疾病的起始因素，但在疾病进展过程中共同作用。线粒体功能障碍和 α-突触核蛋白可能通过多种潜在机制相互作用，从而加剧它们的神经退行性特性。本综述中讨论的候选机制包括自噬、线粒体自噬、线粒体动力学/融合/分裂、氧化应激和活性氧、内质网应激、钙、硝化应激和 α-突触核蛋白寡聚化。
