The analysis of Familial Parkinson's disease gene products and the research for identification of a novel Familial Parkinson's disease gene

帕金森病（PD）是第二大最常见的神经退行性疾病，65岁以上人群的患病率为1%。虽然大多数PD病例是散发的，但现在很清楚遗传因素有助于PD的发病机制。到目前为止，已经确定了家族性帕金森病（FPD）的七个致病基因。考虑到帕金森病等临床表型，FPD基因产物可能具有共同的通路。由于parkin作为E3与泛素通路直接相关，因此该产品也被认为对线粒体起作用。PINK1和DJ-1也与线粒体有关。因此，线粒体是阐明FPD发病机制的靶细胞器。在本研究中，我们发现α-synuclein、parkin、PINK1和DJ-1之间存在共同的通路。相比之下，一半的常染色体隐性FPD在已知的致病基因中没有突变，因此，我们继续进行连锁研究以鉴定新基因。在对具有常染色体隐性遗传模式的迟发性帕金森病致病基因的定位上，可以鉴定出这种形式的帕金森病的几个位点。

Parkinson's disease (PD) is the second most common neurodegenerative disorder with a prevalence of 1% in individuals older than 65 years of age. Although the majority of PD cases are sporadic, it is now clear that genetic factors contribute to the pathogenesis of PD. Until now, seven causative genes for familial PD (FPD) have been identified. Considering the clinical phenotypes such as parkinsonism, it would be possible that FPD gene products share a common pathway. As parkin is direct linked to ubiquitin-pathway as an E3, this product is also thought to function for mitochondria. PINK1 and DJ-1 are also associated with mitochondria. Thus, mitochondrion is a target organella for elucidating the pathogenesis of FPD. In the present study, we found a common pathway between α-synuclein, parkin, PINK1, and DJ-1. In contrast, half of the autosomal recessive FPD showed no mutations in the known causative genes Therefore, we continue to perform the linkage study for identification of a novel gene. On the mapping for a causative gene responsible for late onset PD with autosomal recessive mode of inheritance, a few loci for this form of PD could be identified.