Genetics of Parkinson's disease
Genetics of Parkinson's disease
复制标题
DOI：
10.1093/hmg/6.10.1687
复制
发表时间：
1997-01-01
影响因子：
3.5
通讯作者：
Polymeropoulos, MH
中科院分区：
文献类型：
--
作者：
Nussbaum, RL;Polymeropoulos, MH
在过去的40年里，对帕金森病（PD）的研究主要是流行病学家的领域，他们有兴趣追求疾病与病毒感染或神经毒素等环境因素之间的联系，遗传影响实际上被低估了，因为在后来被证明是不充分和不确定的研究中发现的单卵双胞胎不一致率很高，最近有兴趣在调查遗传因素PD时，它变得越来越明显，积极的家族史是一个主要的危险因素的疾病。与此同时，神经病理学研究也越来越明显地表明，帕金森病的常见特发性形式实际上具有病理相关性，即，Lewy小体广泛分布于黑质、下丘脑、海马、自主神经节和嗅束。尽管在PD家族中连锁的候选基因方法没有得到回报，但全基因组扫描将PD定位到一个具有弥漫性路易体的PD大家族中的4 q21 -23，其中存在候选基因α-突触核蛋白。该基因编码突触前蛋白，已知其肽片段是阿尔茨海默病斑块的成分，alpha-中错义突变的鉴定四个独立的PD家族中的突触核蛋白基因表明，至少有一部分弥漫性路易体的家族性PD是异常蛋白质干扰正常蛋白质降解的结果，导致包涵体的发展，神经元细胞死亡帕金森病中的α-突触核蛋白突变和阿尔茨海默病中的β-淀粉样蛋白和早老素基因突变可能涉及共同的发病机制。
For the past 40 years, research into Parkinson's disease (PD) has been predominantly the province of epidemiologists interested in pursuing the connection between the disease and environmental factors such as viral infection or neurotoxins, Hereditary influences were actually discounted because of a high monozygotic twin discordance rate found in studies that were later shown to be inadequate and inconclusive, There has recently been a resurgence of interest in investigating hereditary factors in PD when it became more and more apparent that a positive family history was a major risk factor for the disease. Meanwhile, it also became increasingly apparent from neuropathological studies that the common, idiopathic form of Parkinson's disease had, in fact, a pathological correlate, i.e., the existence of Lewy bodies, an eosinophilic cytoplasmic inclusion body, distributed diffusely throughout the substnatia nigra, hypothalamus, hippocampus, autonomic ganglia and olfactory tracts. Although candidate gene approaches to linkage in PD families have not been rewarding, a genome wide scan mapped PD to 4q21-23 in one large family with PD with diffuse Lewy bodies, where a candidate gene, alpha-synuclein, resides, This gene encodes a presynaptic protein of which a peptide fragment is known to be a constituent of Alzheimer's disease plaques, The identification of a missense mutation in the alpha-synuclein gene in four independent PD families suggests that at least some fraction of familial PD with diffuse Lewy bodies is the result of an abnormal protein that interferes with normal protein degradation leading to the development of inclusions and ultimately neuronal cell death. There may be common pathogenetic mechanisms involved in alpha-synuclein mutations in PD and beta-amyloid and presenilin gene mutations in Alzheimer's disease.