Institute for Translational Neuroscience, Department of laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN 55455, USA.
Curr Opin Genet Dev. 2012 Jun;22(3):251-5. doi: 10.1016/j.gde.2012.01.001. Epub 2012 Jan 25.
An intriguing set of neurodegenerative disease are the nine disorders caused by the expansion of a unstable trinucleotide CAG repeat where the repeat is located within the coding of the affected gene, that is, the polyglutamine (polyQ) diseases. A gain-of-function mechanism for toxicity in polyQ diseases is widely thought to have a major role in pathogenesis. Yet, the specific nature of this gain-of-function is a matter of considerable discussion. The basic issue concerns whether toxicity stems from the native or normal function of the affected protein versus a novel function induced by polyQ expansion. For at least three of the polyQ disease considerable evidence is accumulating that pathology is mediated by a polyQ-induced exaggeration of a native function of the host protein.
一组有趣的神经退行性疾病是由不稳定的三核苷酸 CAG 重复扩展引起的九种疾病，其中重复位于受影响基因的编码区内，即多聚谷氨酰胺（polyQ）疾病。聚 Q 疾病中毒性的获得性功能机制被广泛认为在发病机制中起主要作用。然而，这种获得性功能的具体性质是一个相当有争议的问题。基本问题是毒性是源于受影响蛋白的天然或正常功能，还是由 polyQ 扩展诱导的新功能。至少有三种 polyQ 疾病的大量证据表明，病理学是由宿主蛋白的 native 功能被 polyQ 诱导夸大所介导的。
