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Use of Pharmaceutical Composition for Manufacturing Drug of Abnormal Polyglutamine-Mediated Diseases

專利類型

發明

專利國別 (專利申請國家)

中華民國

專利申請案號

103100335

專利證號

I 515003

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Use of Pharmaceutical Composition for Manufacturing Drug of Abnormal Polyglutamine-Mediated Diseases

專利所屬機關 (申請機關)

國立臺灣師範大學

獲證日期

2016/01/01

技術說明

小腦萎縮症與致病基因中CAG 重復擴增轉譯出長的多麩醯胺鏈蛋白相關。錯誤摺疊的多麩醯胺蛋白堆積細胞核或質內會導致活性氧分子增加及細胞死亡。因此抑制蛋白聚集及降低活性氧壓力可能抑制衍生的下游有害事件，提供小腦萎縮症的可能治療策略。本研究建立一誘導表現ATXN3/Q75-GFP的Flp-In 293細胞為平台，來檢測中藥脹果甘草(Glycyrrhiza inflata)與活性成份。結果發現脹果甘草及活性成份ammonium glycyrrhizinate、licochalcone A可藉增強粒線體新生及抗氧化功能，來抑制擴增的多麩醯胺蛋白聚集。脹果甘草、ammonium glycyrrhizinate及licochalcone A在表現ATXN3/Q75-GFP且誘導神經分化的SH-SY5Y 細胞中，亦可抑制多麩醯胺蛋白聚集。以上實驗結果顯示中藥脹果甘草及ammonium glycyrrhizinate、licochalcone A能增強粒線體新生及抗氧化功能來抑制多麩醯胺蛋白聚集，在臨床上有潛能被應用來治療小腦萎縮症。 In SCA, the expansions of translated CAG repeats in the disease genes result in long polyQ tracts in the respective proteins. The accumulation of misfolded polyQ proteins is thought to induce oxidative stress and lead to cell death. In this study, we established a high-throughput aggregation screening system using 293 ATXN3/Q75-GFP cells to test the aqueous extract of G. inflata and its constituents. We found the aggregation can be significantly prohibited by G. inflata and its active compounds ammonium glycyrrhizinate and licochalcone A. Meanwhile, G. inflata, ammonium glycyrrhizinate and licochalcone A enhanced mitochondrial biogenesis and antioxidative activity in the same cell models. All of them further reduced the aggregation in neuronal differentiated SH-SY5Y ATXN3/Q75-GFP cells. Our results provide insight into the possible working mechanism of G. inflata in SCA patients.

備註

本部(發文號1100066083)同意貴校110年8月30日師大研合字第1101021150號函申請終止維護專利。(師大)

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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