Hattori Nobutaka
Department of Neurology, Juntendo University School of Medicine.
Rinsho Shinkeigaku. 2004 Nov;44(11):821-3.
In the majority of patients with Parkinson's disease (PD), it is now clear that genetic factors contribute to the pathogenesis of PD, although the contribution of genetic and environmental factors remained to be elucidated. Recently, several genes for familial PD (FPD) based on the single gene defects have been mapped and identified. Alpha-synuclein and UCH-L1 are involved in the dominant form of FPD. In contrast, parkin, DJ-1, and PINK1 are responsible for the recessive form of FPD. The presence of different loci or different causative genes indicates that PD is not a single entity but a highly heterogeneous disorder. However, the functions of causative genes may share common pathways such as an ubiquitin-proteasome pathway, oxidative stress, and mitochondrial dysfunction. Thus, the identification and elucidation of the causative genes should enhance our understanding of the pathogenesis of not only FPD, but also sporadic PD.
目前已明确，在大多数帕金森病（PD）患者中，遗传因素参与了PD的发病机制，尽管遗传因素和环境因素的作用仍有待阐明。最近，基于单基因缺陷的几种家族性PD（FPD）相关基因已被定位和鉴定。α-突触核蛋白和UCH-L1参与FPD的显性形式。相比之下，帕金蛋白、DJ-1和PINK1则与FPD的隐性形式有关。不同基因座或不同致病基因的存在表明，PD并非单一疾病，而是一种高度异质性疾病。然而，致病基因的功能可能共享一些共同途径，如泛素-蛋白酶体途径、氧化应激和线粒体功能障碍。因此，致病基因的鉴定和阐明不仅应加深我们对FPD发病机制的理解，也应加深对散发性PD发病机制的理解。
