Department of Biological Sciences, University of the Sciences, Philadelphia, Pennsylvania 19104.
Department of Biology, Stanford University, Stanford, California 94305.
Cold Spring Harb Perspect Med. 2018 Feb 1;8(2):a024257. doi: 10.1101/cshperspect.a024257.
Transmissible spongiform encephalopathies are infectious neurodegenerative diseases caused by the conversion of prion protein (PrP) into a self-replicating conformation that spreads via templated conversion of natively folded PrP molecules within or between cells. Recent studies provide compelling evidence that prion-like behavior is a general property of most protein aggregates associated with neurodegenerative diseases. Many of these disorders are associated with spontaneous protein aggregation, but genetic mutations can increase the aggregation propensity of specific proteins, including expansion of polyglutamine (polyQ) tracts, which is causative of nine inherited neurodegenerative diseases. Aggregates formed by polyQ-expanded huntingtin (Htt) in Huntington's disease can transfer between cells and seed the aggregation of cytoplasmic wild-type Htt in a prion-like manner. Additionally, prion-like properties of glutamine-rich proteins underlie nonpathological processes in yeast and higher eukaryotes. Here, we review current evidence supporting prion-like characteristics of polyQ and glutamine-rich proteins.
传染性海绵状脑病是由朊病毒蛋白（PrP）转化为自我复制构象引起的传染性神经退行性疾病，该构象通过在细胞内或细胞间天然折叠的 PrP 分子的模板转换进行传播。最近的研究提供了令人信服的证据表明，类朊病毒行为是大多数与神经退行性疾病相关的蛋白质聚集体的普遍特性。这些疾病中有许多与自发的蛋白质聚集有关，但基因突变会增加特定蛋白质的聚集倾向，包括多聚谷氨酰胺（polyQ）片段的扩展，这是导致九种遗传性神经退行性疾病的原因。亨廷顿病中由 polyQ 扩展的亨廷顿蛋白（Htt）形成的聚集体可以在细胞间转移，并以类朊病毒的方式引发细胞质野生型 Htt 的聚集。此外，富含谷氨酰胺的蛋白质的类朊病毒特性是酵母和高等真核生物中非病理过程的基础。在这里，我们回顾了支持 polyQ 和富含谷氨酰胺的蛋白质具有类朊病毒特征的现有证据。
