The Michael J. Fox Foundation for Parkinson's Research, Grand Central Station, P.O. Box 4777, New York, NY 10120, USA.
Biomolecules. 2019 Jul 24;9(8):296. doi: 10.3390/biom9080296.
The role of mitochondria in Parkinson's disease (PD) has been investigated since the 1980s and is gaining attention with recent advances in PD genetics research. Mutations in and PTEN-Induced Putative Kinase 1 () are well-established causes of autosomal recessive early-onset PD. Genetic and biochemical studies have revealed that PINK1 and Parkin proteins function together in the same biological pathway to govern mitochondrial quality control. These proteins have also been implicated in the regulation of innate and adaptive immunity and other mitochondrial functions. Additionally, structural studies on Parkin have delineated an activation mechanism and have identified druggable regions that are currently being explored by academic and industry groups. To de-risk therapeutic development for these genetic targets, The Michael J. Fox Foundation for Parkinson's Research (MJFF) has deployed a strategic funding and enabling framework that brings together the research community to discuss important breakthroughs and challenges in research on PINK1-Parkin biology, supports collaborative initiatives to further our understanding within this field and develops high-quality research tools and assays that are widely available to all researchers. The Foundation's efforts are leading to significant advances in understanding of the underlying biology of these genes, proteins and pathways and in the development of Parkinson's therapies.
自 20 世纪 80 年代以来，人们一直在研究线粒体在帕金森病 (PD) 中的作用，随着 PD 遗传学研究的最新进展，这一作用受到了越来越多的关注。 和 PTEN 诱导的假定激酶 1 () 的突变是常染色体隐性早发性 PD 的明确病因。遗传和生化研究表明，PINK1 和 Parkin 蛋白在同一生物学途径中协同作用，以控制线粒体质量控制。这些蛋白还与先天和适应性免疫以及其他线粒体功能的调节有关。此外，Parkin 的结构研究描绘了一种激活机制，并确定了可药用的区域，目前学术和工业团体正在对此进行探索。为了降低针对这些遗传靶点的治疗开发风险，迈克尔·J·福克斯基金会 (MJFF) 部署了一个战略资助和授权框架，将研究界聚集在一起，讨论 PINK1-Parkin 生物学研究中的重要突破和挑战，支持开展合作倡议以进一步加深我们对该领域的理解，并开发高质量的研究工具和检测方法，供所有研究人员广泛使用。该基金会的努力正在推动这些基因、蛋白和途径的生物学基础以及帕金森病治疗方法的重大进展。
