Peroxisome proliferator-activated receptor γ induces a clearance mechanism for the amyloid-β peptide
Peroxisome proliferator-activated receptor γ induces a clearance mechanism for the amyloid-β peptide
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DOI：
10.1523/jneurosci.3987-04.2004
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发表时间：
2004-12-01
影响因子：
5.3
通讯作者：
De Strooper, B
中科院分区：
文献类型：
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作者：
Camacho, IE;Serneels, L;De Strooper, B
我们研究了过氧化体增殖物激活受体伽马(PPARGamma)是否参与了导致阿尔茨海默病的淀粉样级联反应的调节。使用噻唑烷二酮家族的合成激动剂诱导表达或激活PPARγ可导致神经元和非神经元细胞条件培养液中淀粉样β蛋白(Abeta)水平的急剧下降。PPARGamma不影响与Abeta肽生成有关的任何分泌酶的表达或活性，但会诱导一种快速的细胞结合清除机制，负责将Abeta肽从介质中移除。虽然PPARGamma在中枢神经系统中的表达一般较低，但在炎症过程中诱导PPARGamma的表达可能有利于促进Abeta的清除。我们证实，在原代小鼠混合神经胶质细胞和皮质神经元培养中，PPARγ激活确实可以诱导Abeta清除机制。我们的结果表明，PPAR伽马控制的机制应该作为阿尔茨海默病治疗的潜在药物靶点进行进一步探索。
We investigated whether peroxisome proliferator-activated receptor gamma (PPARgamma) could be involved in the modulation of the amyloid cascade causing Alzheimer's disease. Inducing expression or activating PPARgamma using synthetic agonists of the thiazolinedione family results in a dramatic decrease in the levels of the amyloid-beta(Abeta) peptide in the conditioned medium of neuronal and non-neuronal cells. PPARgamma does not affect expression or activity of any of the secretases involved in the generation of the Abeta peptide but induces a fast, cell-bound clearing mechanism responsible for the removal of the Abeta peptide from the medium. Although PPARgamma expression is generally low in the CNS, induction of PPARgamma expression during inflammation could be beneficial for inducing Abeta clearance. We confirm that the Abeta clearance mechanism can indeed be induced by PPARgamma activation in primary murine-mixed glia and cortical neuronal cultures. Our results suggest that PPARgamma-controlled mechanisms should be explored further as potential drug targets for Alzheimer's disease treatment.