Oxford Parkinson's Disease Centre, Department of Physiology, Anatomy and Genetics, Le Gros Clark Building, University of Oxford, South Parks Road, Oxford, OX1 3QX, UK.
McGill Parkinson Program, Department of Neurology and Neurosurgery, Montreal Neurological Institute and Hospital, McGill University, Montréal, Québec H3A 2B4, Canada.
Trends Biochem Sci. 2015 Apr;40(4):200-10. doi: 10.1016/j.tibs.2015.02.003. Epub 2015 Mar 8.
Parkinson's disease (PD) is a progressive neurodegenerative disorder characterised by the preferential loss of dopaminergic neurons in the substantia nigra. Mitochondrial dysfunction is increasingly appreciated as a key determinant of dopaminergic neuronal susceptibility in PD and is a feature of both familial and sporadic disease, as well as in toxin-induced Parkinsonism. Recently, the mechanisms by which PD-associated mitochondrial proteins phosphatase and tensin homolog deleted on chromosome 10 (PTEN)-induced putative kinase 1 (PINK1) and parkin function and induce neurodegeneration have been identified. In addition, increasing evidence implicates other PD-associated proteins such as α-synuclein (α-syn) and leucine-rich repeat kinase 2 (LRRK2) in mitochondrial dysfunction in genetic cases of PD with the potential for a large functional overlap with sporadic disease. This review highlights how recent advances in understanding familial PD-associated proteins have identified novel mechanisms and therapeutic strategies for addressing mitochondrial dysfunction in PD.
帕金森病（PD）是一种进行性神经退行性疾病，其特征是黑质中多巴胺能神经元的优先丧失。线粒体功能障碍越来越被认为是 PD 中多巴胺能神经元易感性的关键决定因素，并且是家族性和散发性疾病以及毒素诱导的帕金森病的特征。最近，已经确定了与 PD 相关的线粒体蛋白磷酸酶和张力蛋白同源物缺失 10 号染色体（PTEN）诱导的假定激酶 1（PINK1）和 parkin 发挥作用并诱导神经退行性变的机制。此外，越来越多的证据表明，其他与 PD 相关的蛋白质，如α-突触核蛋白（α-syn）和富含亮氨酸重复激酶 2（LRRK2），在具有与散发性疾病大量功能重叠的遗传 PD 病例中，在线粒体功能障碍中起作用。这篇综述强调了理解家族性 PD 相关蛋白的最新进展如何为解决 PD 中线粒体功能障碍确定了新的机制和治疗策略。
