NeuroRegeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Prog Brain Res. 2010;183:21-41. doi: 10.1016/S0079-6123(10)83002-X.
Until recently, genetics was thought to play a minor role in the development of Parkinson's disease (PD). Over the last decade, a number of genes that definitively cause PD have been identified, which has led to the generation of disease models based on pathogenic gene variants that recapitulate many features of the disease. These genetic studies have provided novel insight into potential mechanisms underlying the aetiology of PD. This chapter will provide a profile of the genes conclusively linked to PD and will outline the mechanisms of PD pathogenesis implicated by genetic studies. Mitochondrial dysfunction, oxidative stress and impaired ubiquitin-proteasome system function are disease mechanisms that are particularly well supported by genetic studies and are therefore the focus of this chapter.
直到最近，遗传学被认为在帕金森病（PD）的发展中只起次要作用。在过去的十年中，已经确定了一些明确导致 PD 的基因，这导致了基于致病性基因突变体的疾病模型的产生，这些模型再现了疾病的许多特征。这些遗传研究为 PD 病因学的潜在机制提供了新的见解。本章将介绍与 PD 有明确关联的基因，并概述遗传研究中涉及的 PD 发病机制。线粒体功能障碍、氧化应激和泛素-蛋白酶体系统功能受损是遗传研究特别支持的疾病机制，因此是本章的重点。
