过氧化物酶体增殖物激活受体γ在淀粉样前体蛋白(APP)加工和β-淀粉样蛋白介导的细胞死亡中的作用  

Role of peroxisome proliferator-activated receptor γ in amyloid precursor protein processing and amyloid β-mediated cell death

作　　者：Cristina D’ABRAMO 陈青[1] 

机构地区：[1]中山大学药学院微生物与生化制药室,广东广州510080

出　　处：《中山大学研究生学刊（自然科学与医学版）》2007年第4期82-92,共11页Journal of the Graduates Sun YAT-SEN University(Natural Sciences.Medicine)

摘　　要：最近的数据显示,过氧化物酶体增殖物激活受体γ(Peroxisome proliferator-activated receptorγ,PPARγ)可参与导致阿尔茨海默氏症(Alzheimer's disease,AD)的淀粉样级联的调节。在本研究中我们证明了的PPARγ在培养的细胞中过表达,急剧减少了β-淀粉样蛋白(Amyloid-β,Aβ)的分泌,在转录后水平影响淀粉样前体蛋白(Amyloid precursor protein,APP)的表达。APP下游调节不涉及分泌酶的通路而与对APP泛素化的显著诱导有关。此外,我们还证明了PPARγ能通过降低Aβ的分泌从而保护过氧化氢诱导的细胞坏死。综合起来,我们的研究结果表明了一种新型机制:PPARγ激动剂对神经元的保护作用和由于Aβ的积累所造成的致病作用的机制。Recent data indicate that PPARγ （peroxisome proliferator -activated receptor γ ） could be involved in the modulation of the amyloid cascade causing Alzheimer＇s disease. In the present study we show that PPARγ overexpression in cultured cells dramatically reduced Aβ （amyloid - β） secretion, ＇affecting the expression of the APP （Aβ precursor protein） at a post - transcriptional level. APP down - regulation did not involve the pathway of the secretasesand correlated with a significant induction of APP ubiquitination. Additionally, we demonstrate that PPAR3, was able to protect the cells from H2O2 - induced necrosis by decreasing Aβ secretion. Taken together, our results indicate a novel mechanism at the basis of the neuro protection shown by PPARγ, agonists and an additional pathogenic role for Aβ accumulation.

关 键 词：阿尔兹海默症 非类固醇抗炎药 过氧化物酶体增殖物激活受体Γ Β-淀粉样 淀粉样前体蛋白(APP) 

分 类 号：Q279[生物学—细胞生物学]