Molecular pathogenesis of transmissible spongiform encephalopathy

传染性海绵状脑病的分子发病机制

基本信息

批准号：
08300011
负责人：
YAMANOUCHI Kazuya
金额：
--
依托单位：
Nippon Institute for Biological Science
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (A)
财政年份：
1997
资助国家：
日本
起止时间：
1997 至 1998
项目状态：
已结题

项目摘要

Molecular pathogenesis of prion disease was studied based on the analysis of prion protein (PrP) gene.Several new findings were also obtained from the studies on animal models.Involevement of polymorphisms of PrP gene in the onset of prion disease was indicated, especially in term of correlation of codon 219 with sporadic Creutzfeldt-Jakob disease as a unique feature of Japanese.Correlation of PrP gene mutation with transmission of the disease to mice was also demonstrated.Transgenic mice overexpressing human PrP gene was produced and found to be highly susceptible to CJD.Biochemical profiles of the brain of CJD patient was demonstrated in term of gangliosides.Resistance of PrPSc to proteinase K was shown to correlate with the incubation period of scrapie in mice, and passages in mice brain was suggested to cause increased aggregation of PrPSc.Studies of prion-less neural cells suggested an involvement of apoptosis in the cell death.In vitro model of the conformational change of protein showed temperature-dependent conversion from alpha-helix to beta-sheet.As an animal model of spongiform encephalopathy, zitter rats were studied in terms of zi gene and involvement of super-oxide in pathogenesis.Investigation on spontaneous spongiform encephalopathy in pets and birds could not find such cases.

根据pr蛋白（PRP）基因的分析，研究了prion疾病的分子发病机理。从动物模型的研究中也获得了几个新发现。prp基因的多态性在prion疾病开始时，尤其是在与孢子的cocoration 219相关性的术语中，偶然的cre trc cretrc cretrc crebobfebib crebobjobbjobbjok akak crept akak crept akak akak akak cre trc coreb cretrc-bjok creptip-eport cobobjobgobjobjobgobgobgobjob cre objobgobgobgobjob obj， gene mutation with transmission of the disease to mice was also demonstrated.Transgenic mice overexpressing human PrP gene was produced and found to be highly susceptible to CJD.Biochemical profiles of the brain of CJD patient was demonstrated in term of gangliosides.Resistance of PrPSc to proteinase K was shown to correlate with the incubation period of scrapie in mice, and passages in mice brain was suggested to cause PRPSC的聚集的增加。无临界神经细胞的研究表明，凋亡参与细胞死亡。在蛋白质构象变化的体外模型中，蛋白质的构象变化显示了从α-螺旋体到β-折叠的温度依赖性转化。作为ZITERPARPATENITION的Spongoriform Persivity of Zitter of Ziteent of Zi Gene的动物模型，Zi Gene的范围是研究。宠物和鸟类中的自发海绵状脑病找不到这种情况。