Method for Treating Abnormal β-Amyloid Mediated Diseases

專利類型

發明

專利國別 (專利申請國家)

美國

專利申請案號

14/709,968

專利證號

US 9,795,600

專利獲證名稱

Method for Treating Abnormal β-Amyloid Mediated Diseases

專利所屬機關 (申請機關)

國立臺灣師範大學

獲證日期

2017/10/24

技術說明

阿茲海默氏症會造成持續性的認知能力下降和記憶力減退，是最常見的失智症。細胞外Aβ是阿茲海默氏症病理特點之一的老年瘢塊的主要組成份。已知類澱粉沉積會增加氧化壓力，最後導致神經細胞死亡。故類澱粉沉積的多寡和神經毒性有強烈相關性。因此找出抑制Aβ聚集的抑制物，可能可以幫助治療阿茲海默氏病。本研究利用體外表現Trx-His-Aβ生化模式和Aβ-GFP 293/SH-SY5Y細胞模式，篩選有潛能抑制Aβ聚集的化合物。所檢測的數種合成吲哚喹啉衍生物，顯著增強表現Aβ-GFP的293細胞的綠螢光，並降低細胞中活性氧化物、提高HSPB1伴隨蛋白的表現，及促進表現Aβ-GFP的SH-SY5Y細胞的神經突觸生長。吲哚喹啉衍生物對阿茲海默氏症小鼠大腦初級細胞培養實驗驗證。以上實驗結果顯示吲哚喹啉衍生物能抑制Aβ蛋白聚集，故在臨床上有潛能被應用來治療阿茲海默氏症。 AD is the most prevalent form of dementia associated with progressive cognitive decline and memory loss. In this study Aβ cell-free and cell models with Aβ aggregation were used to screen synthetic indolylquinoline compounds potentially inhibiting Aβ aggregation. Good aggregation-inhibitory effects were seen with the tested synthetic compounds, accompanying with reduced ROS, enhanced chaperone HSPB1 expression and promoted neurite outgrowth. The effect in promoting cell viability and neurite outgrowth were also confirmed with brain primary culture of AD transgenic mice. Our results demonstrate how synthetic indolylquinoline compounds are likely to work in Aβ-aggregation reduction, and provide insight into the possible working mechanism of indolylquinoline compounds in AD patients. These findings may have therapeutic applications in AD.

備註

連絡單位 (專責單位/部門名稱)

產學合作組

連絡電話

77341329

網址