多酚類化合物對醣化蛋白終極產物造成阿茲海默症致病機轉之影響

The effect of polyphenolic compounds for advanced glycation end products (AGEs) cause Alzheimer's disease (AD) pathogenesis

10.6833/CJCU.2012.00166

洪松甫

阿茲海默症 ； 類澱粉前趨蛋白 ； 醣化蛋白終極產物 ； 活性氧化物 ； Resveratrol ； Epigallocatechin-3-gallate ； Curcuminoids ； Advanced glycation end products ； Amyloid precursor protein ； Curcuminoids ； Epigallocatechin-3-gallate ； Reactive oxygen species ； Resveratrol

長榮大學醫學研究所學位論文

2012年

碩士

柯順耀

繁體中文

阿茲海默症(Alzheimer’s disease; AD)主要是腦部神經細胞功能的逐漸喪失所產生的退化性失智症。在患者的腦部發現大量類澱粉前趨蛋白(Amyloid precursor protein; APP)，經由β-secretase和γ-secretase修飾產生類澱粉蛋白(Amyloid beta; Aβ)造成累積而導致神經細胞死亡。研究指出醣化蛋白終極產物(Advanced glycation end products; AGEs)會造成神經細胞傷害。AGEs為梅納反應的產物，是蛋白質經由非酵素性的醣化作用所產生。AGEs所產生的reactive oxygen species (ROS)刺激APP過度表現，進而使Aβ產量增加，而AGEs和Aβ對神經細胞有加成毒性的傷害。研究指出polyphenolic compounds：resveratrol (Res)、epigallocatechin-3-gallate (EGCG)和curcuminoids (Cur)能經由抗氧化能力抑制Aβ生成。故本研究主要探討Res、EGCG和Cur對於AGEs導致的AD致病機轉之影響。結果發現AGEs藉由ROS刺激beta-site APP cleaving enzyme (BACE)和presenilin 1 (PS1)表現增加，而Res、EGCG和Cur減少AGEs所產生的ROS進而調控APP、BACE和PS1的表現。本研究證實Polyphenolic compound能抑制AGEs造成的阿茲海默症致病機轉。

The characteristic of Alzheimer’s disease (AD) is senile plaques in brain which is a neurodegenerative disease. Senile plaques are β-amyloid (Aβ) accumulation. The formation of Aβ which is amyloid precursor protein (APP) cleaved by β-secretase and γ-secretase. Advanced glycation end products (AGEs) are nonenzymatic glycation of proteins from Maillard reaction. Some reports have suggested that AGEs cause reactive oxygen species (ROS). AGEs increase APP expression and Aβ production via ROS. The combination of AGEs and Aβ has additional neurotoxicity. Resveratrol, epigallocatechin-3-gallate (EGCG) and curcuminoids are polyphenolic compounds, and it has been demostrated that polyphenolic compounds reduce Aβ and risk of AD pathogenesis. But the effection between APP metabolic pathway and polyphenolic compounds is unlear. In this study, we propose that resveratrol, EGCG and curcuminoids affect on APP processing pathway regulated by AGEs. The result show that AGEs increase the expression of beta-site APP-cleaving enzyme (BACE) and Presenilin 1 (PS1). More important, polyphenolic compounds would block the effection of AGEs. Therefore, we demonstrate that the development of AGEs causing AD pathogenesis would be decreased by polyphenolic compounds.

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