CHRONIC CNS DISEASE STUDIES--SLOW, LATENT AND TEMPERATE VIRUS INFECTIONS

慢性退行性中枢神经系统病因和发病机制的研究进展 以多发性硬化症为重点的障碍；帕金森氏症、匹克病、亨廷顿氏症和 阿尔茨海默病；西太平洋ALS/PD；核上性瘫痪； 其他老年前期痴呆；脊髓小脑性共济失调；癫痫；慢性 脑炎伴局灶性癫痫；Viliuisk脑病；肌肉 营养不良；慢性精神分裂症；双相精神病、自闭症；SSPE；PML； 透析性脑病；甲肿性克汀病；囊虫病； 颅内肿瘤。 我们把可传播的和不可传播的痴呆定义为脑 由特定宿主的翻译后修饰引起的淀粉样变性 淀粉样原纤维沉积的前体蛋白。我们现在认识到缓慢的 导致库鲁-CJD-瘙痒病复制的非常规病毒 多肽由正常的宿主前体蛋白从头开始形成， 在人类的20号染色体和小鼠的2号染色体上指定。分子 阐明了自发的构型变化到传染性， 基本上是一个结晶学问题，现在正成为我们的主要目标。 家族性CJD的分子遗传分析已经表明有几个 极大地增加(xl0(6))这种可能性的点突变 自发从头转换成一种有感染力的多肽。 微生物学现在必须与一种全新的范式作斗争 在可传播的大脑中复制、感染、致病的病原体 淀粉糖。我们的研究主要集中在分子的阐明上。 具有传染性性质的构型事件 以前正常的宿主前体使用MRI来解释 在产生传递性时发生的配置。 在正常衰老中，阿尔茨海默病(AD)和唐氏综合症 不同的宿主前体蛋白(在人类21号染色体上指定，16 在小鼠体内)是一种细胞分泌的生长因子抑制物。邮寄- 这种正常前体的翻译降解形成了42个氨基 一种酸性淀粉样多肽，聚合后形成 衰老过程中的淀粉样血管病变、淀粉样斑块和神经纤维缠结， AD和唐氏症。所有90多岁的人都会发生这种情况。 遗传、毒性和感染因素可能会加速大脑老化。 淀粉样蛋白沉积。

Studies focus on causes and pathogenesis of chronic degenerative CNS disorders with emphasis on MS; Parkinson's, Pick's, Huntington's and Alzheimer's diseases; ALS/PD of Western Pacific; supranuclear palsy; other presenile dementias; spinocerebellar ataxias; epilepsy; chronic encephalitis with focal epilepsy; Viliuisk encephalopathy; muscular dystrophies; chronic schizophrenia; bipolar psychoses, autism; SSPE; PML; dialysis encephalopathy; goiterous cretinism; cysticercosis; and intracranial neoplasms. We have defined the transmissible and nontransmissible dementias as brain amyloidoses caused by posttranslational modification of a specific host precursor protein to amyloid fibril deposits. We now recognize the slow unconventional viruses causing kuru-CJD-scrapie as replicating polypeptides formed de novo from a normal host precursor protein, specified on chromosome 20 in man and 2 in mice. The molecular elucidation of the spontaneous configurational change to infectivity, basically a crystallographic problem, is now becoming our major target. Molecular genetic analysis of familial CJD already indicates several point mutations which enormously increase (xl0(6))the probability of this spontaneous de novo conversion to an infectious polypeptide. Microbiology must now contend with a totally new paradigm for replicating, infectious, pathogenic agents in the transmissible brain amylodoses. Our studies focus on the elucidation of the molecular configurational events conferring the property of infectivity on a previously normal host precursor using MRI to elucidate the change in configuration which occurs as transmissibility is produced. In normal aging, Alzheimer's disease (AD), and Down's syndrome a different host precursor protein (specified on chromosome 21 in man, 16 in mice) is a cell-excreted inhibitor of growth factors. Post- translational degradation of this normal precursor forms the 42 amino acid amyloid polypeptide which polymerizes to form the deposits of amyloid angiopathy, amyloid plaques and neurofibrillary tangles in aging, AD and Down's. This occurs in all individuals who reach their 90s. Genetic, toxic, and infectious factors may accelerate this aging brain amyloid deposition.