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是研究的重点 以多发性硬化症（MS）为重点的疾病;帕金森氏症、皮克氏症， 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 脑病;肌营养不良;慢性精神分裂症;双相 精神病，孤独症; SSPE; PML;透析性脑病，甲状腺肿 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， 通过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， 引起库鲁-克雅二氏病-痒病的病毒作为复制多肽形成， novo来自正常宿主前体蛋白，在20号染色体上指定， 人和2只小鼠。自发性的分子解释 从构象变化到感染性， 问题，现在正成为我们的主要目标。 分子遗传学分析 家族性克雅氏病已经表明了几个点突变， 极大地增加（x10）这种自发从头发生的概率 转化为感染性多肽。微生物学现在必须 一个全新的模式复制，传染，致病 传染性脑淀粉样变性中的物质 我们的研究集中在 分子构型事件的阐明， 使用CD对先前正常宿主前体的感染性特性 分光光度法、高压EM、MRI来阐明 当产生可传递性时发生的构象。正常 衰老、阿尔茨海默病（AD）和唐氏综合征，不同的宿主 前体蛋白（在人的21号染色体上，在小鼠的16号染色体上指定）是一种 细胞分泌的生长因子抑制剂（蛋白酶连接蛋白II）。 这种正常前体的翻译后降解形成42-氨基 酸性淀粉样多肽，其聚合形成 淀粉样血管病、淀粉样斑块和衰老中的神经纤维缠结， AD和Down's这发生在所有达到90岁的人身上。 遗传、毒性和感染因素可能会加速这种大脑老化 淀粉样沉积

Studies focus on the causes and pathogenesis of chronic degenerative CNS disorders with emphasis on multiple sclerosis (MS); Parkinson's, Pick's, 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 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.