Polymeropoulos M H
Laboratory of Genetic Disease Research, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Ann Neurol. 1998 Sep;44(3 Suppl 1):S63-4. doi: 10.1002/ana.410440710.
Multiple factors have been hypothesized over the years to be contributory and/or causative for Parkinson's disease (PD). Hereditary factors, although originally discounted, have recently emerged in the focus of PD research. The study of a large Italian family with PD using a genome scan approach led to the mapping of a PD susceptibility gene to the 4q21-q23 genomic region, where the gene for alpha-synuclein was previously mapped. Mutation analysis of the alpha-synuclein in four unrelated families with PD revealed a missense mutation segregating with the illness. Alpha-synuclein is an abundant presynaptic protein in the human brain with unknown function. It is conceivable that the mutation identified in the PD families may result in self-aggregation and/or decreased degradation of the protein, leading to the development of intracytoplasmic inclusion bodies and eventually to neuronal cell death. Moreover, the discovery of a mutation in the synuclein gene may offer us new insights in the understanding of the pathways that lead to neuronal degeneration.
多年来，人们一直假设有多种因素促成和/或导致帕金森病（PD）。遗传因素虽然最初被排除在外，但最近已成为PD研究的焦点。对一个患有PD的意大利大家庭采用基因组扫描方法进行研究，结果将一个PD易感基因定位到4q21 - q23基因组区域，此前α-突触核蛋白基因也被定位在此处。对四个无亲缘关系的PD家族中的α-突触核蛋白进行突变分析，发现一个错义突变与该病共分离。α-突触核蛋白是人类大脑中一种丰富的突触前蛋白，功能未知。可以想象，在PD家族中鉴定出的突变可能导致该蛋白的自我聚集和/或降解减少，从而导致胞质内包涵体的形成，并最终导致神经元细胞死亡。此外，突触核蛋白基因突变的发现可能为我们理解导致神经元变性的途径提供新的见解。
