NeuroRegeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Annu Rev Genomics Hum Genet. 2011;12:301-25. doi: 10.1146/annurev-genom-082410-101440.
Genetic studies have provided valuable insight into the pathological mechanisms underlying Parkinson's disease (PD). The elucidation of genetic components to what was once largely considered a nongenetic disease has given rise to a multitude of cell and animal models enabling the dissection of molecular pathways involved in disease etiology. Here, we review advances obtained from models of dominant mutations in α-synuclein and LRRK2 as well as recessive PINK1, parkin and DJ-1 mutations. Recent genome-wide association studies have implicated genetic variability at two of these loci, α-synuclein and LRRK2, as significant risk factors for developing sporadic PD. This, coupled with the established role of mitochondrial impairment in both familial and sporadic PD, highlights the likelihood of common mechanisms fundamental to the etiology of both.
遗传研究为帕金森病（PD）的病理机制提供了有价值的见解。阐明曾经被认为主要是遗传疾病的遗传成分，产生了多种细胞和动物模型，使人们能够剖析疾病发病机制中涉及的分子途径。在这里，我们回顾了由α-突触核蛋白和 LRRK2 中的显性突变以及 PINK1、parkin 和 DJ-1 隐性突变模型获得的进展。最近的全基因组关联研究表明，这些基因座中的两个基因，即α-突触核蛋白和 LRRK2，遗传变异性是发生散发性 PD 的重要危险因素。这一点，加上线粒体损伤在家族性和散发性 PD 中的既定作用，突出了两者发病机制中存在共同机制的可能性。
