醫藥組成物於製備不正常多麩醯胺聚集類疾病之藥物上之用途Method for Treating Abnormal Polyglutamine-Mediated Disease

專利類型

發明

專利國別 (專利申請國家)

美國

專利申請案號

14/331,613

專利證號

US 9,463,197 B2

專利獲證名稱

醫藥組成物於製備不正常多麩醯胺聚集類疾病之藥物上之用途Method for Treating Abnormal Polyglutamine-Mediated Disease

專利所屬機關 (申請機關)

國立臺灣師範大學

獲證日期

2016/10/11

技術說明

在多麩醯胺居間的疾病，致病基因中擴增CAG重復轉譯出長的多麩醯胺鏈，導致多麩醯胺蛋白聚集、堆積及細胞死亡。本研究發現trehalose、lactulose及melibiose可抑制擴增的多麩醯胺蛋白聚集，同時trehalose、lactulose、melibiose皆可活化細胞自噬，並降低表現TBP/Q79-GFP且誘導神經分化的SH-SY5Y細胞形成聚集。對Purkinje細胞的促進神經突觸生長及抑制聚集，亦可於SCA17小鼠小腦初級細胞/海馬迴切片培養實驗驗證。以上實驗結果顯示lactulose、melibiose及trehalose/validoxylamine A合併使用在臨床上有潛能被應用來治療小腦萎縮症及與蛋白聚集相關的疾病。 In polyQ-mediated disorders, the expansions of translated CAG repeats in the disease genes result in long polyQ tracts in the respective proteins, leading to intracellular accumulation of aggregated polyQ proteins and cell death. In this study, we found the aggregation can be significantly prohibited by trehalose, lactulose and melibiose. Meanwhile, trehalose, lactulose and melibiose up-regulated autophagy in the same cell models and reduced the aggregation in neuronal differentiated SH-SY5Y TBP/Q79-GFP cells. The effect in promoting neurite outgrowth and reduction of aggregation on Purkinje cells were also confirmed with cerebellar primary and slice cultures of SCA17 transgenic mice. Further studies revealed that validoxylamine A specifically inhibits trehalase at IC50 value 14.4 nM. Together our results suggested lactulose, melibiose or combined administration of trehalose and validoxylamine A are potential therapeutics for the protein deposition-mediated diseases.

備註

連絡單位 (專責單位/部門名稱)

產學合作組

連絡電話

77341329

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