Laboratory of Bacterial and TSE Agents, Division of Emerging Transfusion Transmitted Diseases, Office of Blood Research and Review, Center for Biologics Evaluation and Research, Food and Drug Administration, 1401 Rockville Pike, HFM-313, Rockville, MD 20852, USA.
J Gen Virol. 2014 Jul;95(Pt 7):1612-1618. doi: 10.1099/vir.0.062083-0. Epub 2014 Apr 25.
Proteins aggregate in several slowly progressive neurodegenerative diseases called 'proteinopathies'. Studies with cell cultures and transgenic mice overexpressing mutated proteins suggested that aggregates of one protein induced misfolding and aggregation of other proteins as well - a possible common mechanism for some neurodegenerative diseases. However, most proteinopathies are 'sporadic', without gene mutation or overexpression. Thus, proteinopathies in WT animals genetically close to humans might be informative. Squirrel monkeys infected with the classical bovine spongiform encephalopathy agent developed an encephalopathy resembling variant Creutzfeldt-Jakob disease with accumulations not only of abnormal prion protein (PrP(TSE)), but also three other proteins: hyperphosphorylated tau (p-tau), α-synuclein and ubiquitin; β-amyloid protein (Aβ) did not accumulate. Severity of brain lesions correlated with spongiform degeneration. No amyloid was detected. These results suggested that PrP(TSE) enhanced formation of p-tau and aggregation of α-synuclein and ubiquitin, but not Aβ, providing a new experimental model for neurodegenerative diseases associated with complex proteinopathies.
在几种称为“蛋白病”的缓慢进展性神经退行性疾病中，蛋白质会聚集。细胞培养和过表达突变蛋白的转基因小鼠的研究表明，一种蛋白质的聚集体也会诱导其他蛋白质的错误折叠和聚集 - 这可能是一些神经退行性疾病的共同机制。然而，大多数蛋白病是“散发性”的，没有基因突变或过表达。因此，与人类遗传上接近的 WT 动物中的蛋白病可能具有信息性。感染经典牛海绵状脑病病原体的松鼠猴会发展出类似于变异克雅氏病的脑病，不仅积累异常朊病毒蛋白（PrP(TSE)），还积累另外三种蛋白质：过度磷酸化的 tau（p-tau）、α-突触核蛋白和泛素；β-淀粉样蛋白（Aβ）不会积累。脑损伤的严重程度与海绵状变性相关。未检测到淀粉样蛋白。这些结果表明，PrP(TSE)增强了 p-tau 的形成和α-突触核蛋白和泛素的聚集，但不增强 Aβ 的聚集，为与复杂蛋白病相关的神经退行性疾病提供了新的实验模型。
