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

中枢神经系统慢性退行性变的病因和发病机制 以MS为重点的疾病;帕金森氏症、皮克氏症、亨廷顿氏症和 阿尔茨海默病;西太平洋ALS-PD;核上性麻痹;其他 早老性痴呆;脊髓小脑共济失调;癫痫;慢性 脑炎伴局灶性癫痫;维留伊斯克脑病;肌性 营养不良;慢性精神分裂症;双相性精神病，孤独症; SSPE; PML; 透析性脑病;甲状腺肿性克汀病;囊虫病;和 颅内肿瘤 我们已经将传染性和非传染性痴呆定义为脑 由特定宿主的翻译后修饰引起的淀粉样变性 淀粉样纤维沉积的前体蛋白。 我们现在认识到 引起库鲁-克雅二氏病-羊瘙痒病的非常规病毒 由正常宿主前体蛋白从头形成的多肽， 在人的20号染色体和小鼠的2号染色体上特异性。 分子 阐明感染性的自发构型变化， 基本上是一个晶体学问题，现在成为我们的主要目标。 家族性克雅氏病的分子遗传学分析已经表明了几点 突变极大地增加了（x10/6）这种可能性， 自发从头转化为感染性多肽。 微生物 现在必须面对一个全新的复制，传染， 传染性脑淀粉样变性中的致病因子。 我们的研究 着重于分子构型事件的阐明 使以前正常的宿主具有传染性的 使用MRI来阐明发生的配置变化的前体 随着传播性的产生。 在正常衰老、阿尔茨海默病（AD）和唐氏综合征中， 不同的宿主前体蛋白（在人的21号染色体上，在人的16号染色体上， 小鼠）是细胞分泌的生长因子抑制剂。 翻译后 这种正常前体的降解形成42 -氨基酸淀粉样蛋白 聚合形成淀粉样血管病沉积物的多肽， 淀粉样斑块和神经纤维缠结在老化，AD和唐氏症。 这 发生在所有90多岁的人身上。 遗传的，有毒的， 感染因素可能加速这种老化的脑淀粉样蛋白沉积。

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.