Gasser Thomas
Department of Neurodegenerative Diseases, Hertie-Institute for Clinical Brain Research, University of Tübingen, Hoppe-Seyler Str. 3, 72076 Tübingen, Germany.
Expert Rev Mol Med. 2009 Jul 27;11:e22. doi: 10.1017/S1462399409001148.
Over the past few years, genetic findings have changed our views on the molecular pathogenesis of Parkinson disease (PD), as mutations in a growing number of genes have been found to cause monogenic forms of the disorder. These mutations cause neuronal dysfunction and neurodegeneration either by a toxic gain of function, as in the case of the dominant forms of monogenic PD caused by mutations in the genes for alpha-synuclein or LRRK2, or by a loss of an intrinsic protective function, as is likely for the recessive PD genes parkin (PRKN), PINK1 and DJ-1. Evidence is emerging that at least some of the pathways uncovered in the rare monogenic forms of PD may play a direct role in the aetiology of the common sporadic disorder and that variants of the respective genes contribute to the risk of developing the disease. These findings will allow the search for new treatment strategies that focus on the underlying molecular pathophysiology, rather than simply on ameliorating symptoms.
在过去几年中，遗传学研究结果改变了我们对帕金森病（PD）分子发病机制的看法，因为已发现越来越多的基因突变会导致该疾病的单基因形式。这些突变通过功能获得性毒性导致神经元功能障碍和神经退行性变，如由α-突触核蛋白或LRRK2基因中的突变引起的显性单基因PD形式，或通过内在保护功能丧失导致，隐性PD基因parkin（PRKN）、PINK1和DJ-1可能就是这种情况。越来越多的证据表明，至少在罕见的单基因形式的PD中发现的一些途径可能在常见散发性疾病的病因中起直接作用，并且各自基因的变体有助于增加患该疾病的风险。这些发现将有助于寻找新的治疗策略，这些策略专注于潜在的分子病理生理学，而不仅仅是缓解症状。
