Therapy for the polyglutamine diseases via selection of oligomer inhibitors using new technologies SPR & FCS

多谷氨酰胺（polyQ）疾病是由大脑中蛋白质积累引起的神经系统疾病。最近的研究表明，在其积累之前形成的称为寡聚物的蛋白质复合物是有毒的物种。为了建立针对多q疾病的治疗方法，我们使用新技术SPR和FCS筛选特异性结合多q疾病致病蛋白并抑制寡聚物形成的化学物质。我们发现QSI-1在体外和细胞培养中发挥作用，对多q病蝇模型的神经表型和蛋白质积累也有治疗作用。此外，对多q病小鼠模型给予QSI-1可改善神经系统症状。我们的研究结果表明，在建立多q疾病的治疗方法方面取得了巨大的进步。此外，我们筛选候选治疗药物的策略可用于由低聚物形成引起的其他神经系统疾病。

The polyglutamine(polyQ) diseases are neurological diseases caused by the accumulation of proteins in the brain. Recent studies show that protein complexes named oligomers that are formed prior to their accumulation are the toxic species. Towards establishing a therapy against the polyQ diseases, we screened for chemicals that specifically bind to the disease-causing protein of the polyQ diseases and also inhibit oligomer formation, using the new technologies SPR and FCS. We found that QSI-1, which exerted effects in vitro and in cell culture also exerted therapeutic effects against the neurological phenotypes and protein accumulation of a polyQ disease fly model. Furthermore, administration of QSI-1 to polyQ disease mouse models resulted in amelioration of the neurological symptoms. Our results demonstrate a great advancement towards establishing a therapy for the polyQ diseases. Furthermore, our strategy of screening for therapeutic candidates can be utilized for other neurological diseases that are caused by oligomer formation.