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Study on pathologic mechanism of wild or mutant prion protein gene.

野生或突变朊病毒蛋白基因病理机制的研究。

基本信息

批准号：
05454660
负责人：
KITAMOTO Tetsuyuki
金额：
$ 4.48万
依托单位：
KYUSHU UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1993
资助国家：
日本
起止时间：
1993 至 1994
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-05454660/
关键词：
Creutzfeldt-Jakob disease Prion protein point mutation 点変異挿入変異

项目摘要

Recent molecular genetic studies revealed that the human prion protein (PrP) gene has a large repertoire of polymorphisms and mutations. Each variant PrP seems to correspond to a distinct type of prion diseases. On this project, we found out 6 new mutations and 3 insertional mutations of PrP gene. It is useful to classify prion diseases into plaque type or non-plaque type, based on the distribution of PrP in the central nervous system. The variant PrP including codon 102, codon 102/219, codon 105, codon 129 Valine, codon 145 and insertional polymorphisms belong to the plaque type prion diseases, whereas the wild-type PrP (codon 129 Methionine) and the variants including codon 180, codon 200, and codon 232 mutations belong to the non-plaque type (synaptic type). The non-plaque type prion diseases showed a rapidly progressive dementia, myoclonus and periodic synchronous discharges in the electroencephalogram, and in the pathological findings diffuse gray matter PrP accumulations including the synaptic structures. The plaque type prion diseases showed a long clinical course without myoclonus and periodic synchronous discharges, and the major PrP accumulation sites were extracellular PrP plaques. The distribution of PrP deposits in the central nervous system influences the clinical and pathological aspects of prion diseases. Thus, PrP accumulations may play a central role in the pathogenesis of prion diseases.

最近的分子遗传学研究表明，人朊蛋白（PrP）基因具有大量的多态性和突变。每一种PrP变体似乎对应于一种不同类型的朊病毒疾病。本课题共发现PrP基因的6个新突变和3个插入突变。根据PrP在中枢神经系统中的分布，将朊病毒疾病分为斑块型和非斑块型是有用的。包括密码子102、密码子102/219、密码子105、密码子129缬氨酸、密码子145和插入多态性的变体PrP属于斑块型朊病毒病，而野生型PrP（密码子129甲基化）和包括密码子180、密码子200和密码子232突变的变体PrP属于非斑块型（突触型）。非斑块型朊病毒病脑电图表现为快速进展性痴呆、肌阵挛和周期性同步放电，病理表现为包括突触结构在内的弥漫性灰质PrP积聚。斑块型朊病毒病病程长，无肌阵挛和周期性同步放电，主要聚集部位为细胞外朊蛋白斑块。PrP沉积物在中枢神经系统中的分布影响朊病毒疾病的临床和病理方面。因此，朊蛋白的积累可能在朊病毒疾病的发病机制中发挥重要作用。