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; ALS ;西太平洋ALS-PD;核上型 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; 肌营养不良症;慢性精神分裂症;双相性精神病，孤独症; 透析性脑病，甲状腺肿性克汀病;囊虫病; 和颅内肿瘤。 我们已经定义了传染性和 非传染性痴呆，如脑淀粉样变性， 特定宿主前体蛋白的翻译后修饰， 淀粉样纤维沉积。我们现在认识到缓慢的非传统病毒 引起库鲁-克雅二氏病-痒病的复制多肽， 一种正常宿主前体蛋白，在人类20号染色体上特异性表达， 2在老鼠自发构象的分子解析 传染性的改变，基本上是一个晶体学问题， 成为我们的主要目标。 家族性克雅氏病的分子遗传学分析 已经表明了几个点突变，这些突变极大地增加了（x10 ）这种自发从头转化为感染性疾病的概率 多肽。微生物学现在必须与一个全新的范式作斗争 在可传播的大脑中复制传染性病原体 淀粉样变性 我们的研究集中在分子的阐明 配置事件赋予一个人传染性的属性， 使用CD分光光度法，高压 EM、MRI来阐明当 传播性产生了。在正常衰老中，阿尔茨海默病（AD）， 和唐氏综合征，一种不同的宿主前体蛋白（在 人类21号染色体，小鼠16号染色体）是一种细胞分泌的生长抑制剂 蛋白酶nexin II）。这种正常的翻译后降解 前体形成42个氨基酸的淀粉样多肽， 形成淀粉样血管病、淀粉样斑块和 老年痴呆症和唐氏症的神经系统紊乱这发生在所有 90多岁的人。 遗传、毒性和感染因素 可能会加速大脑淀粉样蛋白的沉积

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 ; 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, goitrous 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 conformational 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 ) 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 amyloidoses. Our studies focus on the elucidation of the molecular configurational events conferring the property of infectivity on a previously normal host precursor using CD spectrophotometry, high-voltage EM, MRI to elucidate the change in conformation 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 (protease nexin II). Posttranslational 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.