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

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的分子遗传学分析已经表明了几点 极大地增加(x10/6)这种可能性的突变 自发从头转换成一种有感染力的多肽。微生物学 现在必须应对一种全新的复制、传染、 传播性脑部淀粉中的致病物质。我们的研究 重点阐明分子构型事件 对先前正常的宿主赋予传染性的性质 使用MRI来解释所发生的构型变化的前驱 随着传播性的产生。 在正常衰老、阿尔茨海默病(AD)和唐氏综合症中， 不同的宿主前体蛋白(在人类21号染色体上指定，在16号染色体上 小鼠)是一种细胞分泌的生长因子抑制物。翻译后 这种正常前体的降解形成了42个氨基酸的淀粉样蛋白 聚合形成淀粉样血管病变沉积物的多肽， 衰老、阿尔茨海默病和唐氏症中的淀粉样斑块和神经纤维缠结。 所有90多岁的人都会发生这种情况。遗传的、有毒的和 感染因素可能会加速这种老化的大脑淀粉样蛋白沉积。

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 post-translational 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 (x10/6) 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.