以amyloid-β聚集為目標的阿茲海默氏症治療策略

Therapeutic Strategy Targeting Amyloid-β Aggregation for Alzheimer's Disease

黃鉦翔(Chen-Hsiang Huang) ； 林志信(Chih-Hsin Lin) ； 李承榆(Cheng-Yu Lee) ； 簡虹琪(Hong-Chi Chien) ； 陳廷碩(Ting-Shou Chen) ； 李琦玫(Chi-Mei Lee) ； 李桂楨(Guey-Jen Lee-Chen)

《Bio Formosa》 48卷 (2013/06) Pp. 55-62

https://doi.org/10.6248/BF.2013.48.07

摘要

阿茲海默氏症是最常見的漸進性的認知能力下降和記憶力減退的失智症，病理上此疾病的特點是細胞外Aβ胜肽的類澱粉斑塊沉積和細胞內神經纖維糾結。已知類澱粉沉積會增加氧化壓力、細胞興奮性毒性、能源消耗和細胞凋亡，最後導致神經細胞死亡。先前Aβ42-GFP融合蛋白的研究顯示，Aβ42胜肽的聚集可反應在相連的GFP蛋白之綠螢光亮度上。故本研究建立表現Aβ42-GFP融合蛋白的Tet-On 293細胞作為篩檢平台，藉測定綠螢光亮度增加情形，來檢測可延緩或抑制Aβ聚集的抑制物。首先檢測作為正控制組的薑黃素，可顯著增加綠螢光亮度。進一步以工研院提供的植物藥前處理細胞8小時後誘導Aβ42-GFP表現三天，發現NTNU-043、057、059、071等植物藥可顯著增加綠螢光亮度，並伴隨著伴隨蛋白HSPB1表現的增加。我們的結果顯示上述植物藥可抑制Aβ聚集及其可能的機制，此篩檢平台可用來篩檢更多有潛能治療阿茲海默氏症的植物藥。

關鍵字

阿茲海默氏病 ； 類澱粉聚集 ； 細胞模式 ； 植物藥篩檢

並列摘要

Alzheimer's disease (AD) is the most prevalent form of dementia associated with progressive cognitive decline and memory loss. Molecular hallmarks of the disease are characterized by extracellular Aβ plaques and intracellular neurofibrillary tangles (NFTs). Aβ deposition causes neuronal death via a number of possible mechanisms including oxidative stress, excytotoxicity, energy depletion and apoptosis. Previously Aβ42 was fused to the N-terminus of GFP to couple the aggregation state with the fluorescence of GFP. In the present study, Aβ42-GFP are used to generate Tet-On 293 cell clone as screening platforms. Inhibitors that retard or block Aβ aggregation can be distinguished by increasing fluorescence on Tet-On 293 cells. As a positive control, curcumin increased green fluorescence significantly. Treatment of herbal medicines NTNU-043, 057, 059 and 071 (provided by Industrial Technology Research Institute of Taiwan) resulted in significant increased fluorescence on Tet-On Aβ-GFP cells, accompanying with enhanced HSPB1 chaperone expression. Our results demonstrate how these herbal medicines are likely to work on Aβ-aggregation reduction, and provide insight into the possible working mechanism in AD. We anticipate our assay to be a starting point for screening more potential herbs for the treatment of AD.

並列關鍵字

Alzheimer's disease ； Aβ aggregation ； cell model ； herbal medicine screen