Role of peroxisome proliferator-activated receptor γ in amyloid precursor protein processing and amyloid β-mediated cell death
Role of peroxisome proliferator-activated receptor γ in amyloid precursor protein processing and amyloid β-mediated cell death
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DOI：
10.1042/bj20050560
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发表时间：
2005-11-01
影响因子：
4.1
通讯作者：
Ricciarelli, R
中科院分区：
文献类型：
--
作者：
d'Abramo, C;Massone, S;Ricciarelli, R
最近的数据表明，PPARγ(过氧化物酶体增殖物激活受体γ)可能参与了导致阿尔茨海默病的淀粉样级联反应的调节。在目前的研究中，我们发现PPARγ在培养细胞中的过表达显著减少了Aβ(淀粉样β蛋白)的分泌，在转录后水平影响了Aβ前体蛋白(APP)的表达。APP下调不涉及分泌酶的途径，与APP泛素化的显著诱导相关。此外，我们还证明了PPAR-γ能够通过减少Aβ的分泌来保护细胞免受过氧化氢诱导的坏死。综上所述，我们的结果表明了一种新的机制，其基础是PPAR伽马激动剂表现出的神经保护和Aβ积聚的额外致病作用。
Recent data indicate that PPAR gamma (peroxisome proliferator-activated receptor gamma) could be involved in the modulation of the amyloid cascade causing Alzheimer's disease. In the present study we show that PPAR gamma overexpression in cultured cells dramatically reduced A beta (amyloid-beta) secretion, affecting the expression of the APP (A beta precursor protein) at a post-transcriptional level. APP down-regulation did not involve the pathway of the secretases, and correlated with a significant induction of APP ubiquitination. Additionally, we demonstrate that PPAR gamma was able to protect the cells from H2O2-induced necrosis by decreasing A beta secretion. Taken together, our results indicate a novel mechanism at the basis of the neuroprotection shown by PPAR gamma agonists and an additional pathogenic role for A beta accumulation.