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

多聚谷氨酰胺（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低聚物的蛋白质复合物是有毒物质。为了建立针对polyQ疾病的疗法，我们使用SPR和FCS新技术筛选了特异性结合polyQ疾病的致病蛋白并抑制寡聚体形成的化学物质。我们发现，在体外和细胞培养中发挥作用的QSI-1也对polyQ疾病苍蝇模型的神经表型和蛋白质积累发挥治疗作用。此外，向polyQ疾病小鼠模型施用QSI-1导致神经症状的改善。我们的研究结果证明了建立polyQ疾病治疗方法的巨大进步。此外，我们筛选治疗候选物的策略可用于由寡聚体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.