Hofer Anne, Gasser Thomas
Department of Neurodegenerative Diseases, Hertie-Institute for Clinical Brain Research, University of Tuebingen, 72076 Tuebingen, Germany.
J Mol Neurosci. 2004;24(3):417-24. doi: 10.1385/JMN:24:3:417.
Over the last few years, several genes for rare, monogenically inherited forms of Parkinson's disease (PD) have been mapped and/or cloned. In dominant families, mutations have been identified in the gene for alpha-synuclein. Aggregation of this protein in intracellular inclusions (Lewy bodies) may be crucial in the molecular pathogenesis of the disease. Three genes have been identified to cause autosomal-recessive early-onset parkinsonism: parkin, DJ1, and PINK1. These genes are thought to be involved in the proteasomal protein degradation pathway, in the cell's response to oxidative stress, and in mitochondrial function, respectively. It is therefore concluded that these cellular mechanisms may play an important role in the degenerative process of PD. There is also accumulating evidence that genetic factors play a role in the common sporadic form of PD, however their precise nature remains unknown.
在过去几年中，已对几种中绘制图谱和/或克隆了几种导致罕见的单基因遗传性帕金森病（PD）的基因。在显性遗传家族中，已在α-突触核蛋白基因中鉴定出突变。这种蛋白质在细胞内包涵体（路易小体）中的聚集可能在该疾病的分子发病机制中起关键作用。已确定三个基因可导致常染色体隐性早发性帕金森综合征：帕金森病蛋白、DJ1和PINK1。这些基因分别被认为参与蛋白酶体蛋白降解途径、细胞对氧化应激的反应以及线粒体功能。因此得出结论，这些细胞机制可能在帕金森病的退行性过程中起重要作用。也有越来越多的证据表明遗传因素在常见的散发性帕金森病中起作用，然而其确切性质仍然未知。
