Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, Indiana, USA.
Prog Mol Biol Transl Sci. 2012;107:125-88. doi: 10.1016/B978-0-12-385883-2.00011-4.
Mutations in SNCA, PINK1, parkin, and DJ-1 are associated with autosomal-dominant or autosomal-recessive forms of Parkinson's disease (PD), the second most common neurodegenerative disorder. Studies on the structural and functional properties of the corresponding gene products have provided significant insights into the molecular underpinnings of familial PD and the much more common sporadic forms of the disease. Here, we review recent advances in our understanding of four PD-related gene products: α-synuclein, parkin, PINK1, and DJ-1. In Part 1, we review new insights into the role of α-synuclein in PD. In Part 2, we summarize the latest developments in understanding the role of mitochondrial dysfunction in PD, emphasizing the role of the PINK1/parkin pathway in regulating mitochondrial dynamics and mitophagy. The role of DJ-1 is also discussed. In Part 3, we point out converging pathways and future directions.
SNCA、PINK1、parkin 和 DJ-1 的突变与常染色体显性或常染色体隐性帕金森病 (PD) 相关，PD 是第二常见的神经退行性疾病。对相应基因产物的结构和功能特性的研究为家族性 PD 以及更为常见的散发性疾病的分子基础提供了重要的见解。在这里，我们回顾了对四种与 PD 相关的基因产物：α-突触核蛋白、parkin、PINK1 和 DJ-1 的理解的最新进展。在第 1 部分中，我们回顾了对 α-突触核蛋白在 PD 中的作用的新见解。在第 2 部分中，我们总结了理解 PD 中线粒体功能障碍作用的最新进展，强调了 PINK1/parkin 途径在调节线粒体动力学和线粒体自噬中的作用。DJ-1 的作用也进行了讨论。在第 3 部分中，我们指出了趋同途径和未来方向。
