PDF(Pubmed)
Abstract：
Parkinson\'s disease (PD) is the second most common neurodegenerative disease with currently no cure. Most PD cases are sporadic, and about 5-10% of PD cases present a monogenic inheritance pattern. Mutations in more than 20 genes are associated with genetic forms of PD. Mitochondrial dysfunction is considered a prominent player in PD pathogenesis. Post-translational modifications (PTMs) allow rapid switching of protein functions and therefore impact various cellular functions including those related to mitochondria. Among the PD-associated genes, Parkin, PINK1, and LRRK2 encode enzymes that directly involved in catalyzing PTM modifications of target proteins, while others like α-synuclein, FBXO7, HTRA2, VPS35, CHCHD2, and DJ-1, undergo substantial PTM modification, subsequently altering mitochondrial functions. Here, we summarize recent findings on major PTMs associated with PD-related proteins, as enzymes or substrates, that are shown to regulate important mitochondrial functions and discuss their involvement in PD pathogenesis. We will further highlight the significance of PTM-regulated mitochondrial functions in understanding PD etiology. Furthermore, we emphasize the potential for developing important biomarkers for PD through extensive research into PTMs.
摘要：
帕金森病（PD）是第二常见的神经退行性疾病，目前尚无治愈方法。大多数PD病例是零星的，约5-10%的PD病例呈现单基因遗传模式。超过20个基因的突变与PD的遗传形式有关。线粒体功能障碍被认为是PD发病机理中的重要角色。翻译后修饰（PTM）允许蛋白质功能的快速转换，因此影响各种细胞功能，包括与线粒体相关的功能。在PD相关基因中，Parkin,PINK1和LRRK2编码直接参与催化靶蛋白PTM修饰的酶，而其他人喜欢α-突触核蛋白，FBXO7、HTRA2、VPS35、CHCHD2和DJ-1进行了大量的PTM改性，随后改变线粒体功能。这里,我们总结了与PD相关蛋白相关的主要PTM的最新发现，作为酶或底物，被证明可以调节重要的线粒体功能，并讨论它们在PD发病机理中的参与。我们将进一步强调PTM调节的线粒体功能在理解PD病因中的重要性。此外，我们强调通过广泛的PTM研究开发PD重要生物标志物的潜力.
