化合物用於製備治療不正常乙型-澱粉樣蛋白聚集類疾病之醫藥組成物之用途

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

105125668

專利證號

I 633881

專利獲證名稱

化合物用於製備治療不正常乙型-澱粉樣蛋白聚集類疾病之醫藥組成物之用途

專利所屬機關 (申請機關)

國立臺灣師範大學

獲證日期

2018/09/01

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β-amyloid (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。本研究利用可誘導Aβ-GFP 表現的293/SH-SY5Y細胞模式作為平台，來篩選有潛能抑制Aβ聚集的甘草查爾酮A及香豆素衍生物。當測試物延緩或抑制Aβ聚集時，細胞的GFP螢光會增強。所測試的5種合成衍生物，皆顯著增強表現Aβ-GFP 293細胞的綠螢光，降低細胞中活性氧化物及凋亡蛋白酶3活性，及促進表現Aβ-GFP SH-SY5Y細胞的神經突生長。以上實驗結果顯示新穎甘草查爾酮A及香豆素衍生物能抑制Aβ蛋白聚集及具神經保護作用，故在臨床上有潛能被應用來治療阿茲海默氏症。 Alzheimer’s disease (AD) is the most prevalent form of dementia associated with progressive cognitive decline and memory loss. Extracellular Aβ is a major constituent of senile plaques, one of the hallmarks of AD. Aβ deposition causes neuronal death. Therapeutic approaches to identify novel Aβ aggregate reducers will be effective for the disease treatment. In this study Aβ-GFP 293/SH-SY5Y cell models with Aβ aggregation were used to screen synthetic licochalcone A and coumarin derivatives potentially inhibiting Aβ aggregation. Good aggregation-inhibitory effects were seen in Tet-On 293 cells treated with the test compounds, accompanying with reduced reactive oxygen species and caspase-3 activity. These test compounds also promoted neurite outgrowth in Tet-On SH-SY5Y cells. The study results demonstrated that licochalcone A and coumarin derivatives are likely to work in Aβ aggregation reduction and neuroprotection, providing insight into the possible applications in AD treatment.

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產學合作組

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77341329

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