Oxidative stress increases levels of endogenous amyloid-β peptides secreted from primary chick brain neurons
Oxidative stress increases levels of endogenous amyloid-β peptides secreted from primary chick brain neurons
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DOI：
10.1111/j.1474-9726.2008.00423.x
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发表时间：
2008-10-01
期刊：
影响因子：
7.8
通讯作者：
Lim, Yun-An
中科院分区：
文献类型：
--
作者：
Goldsbury, Claire;Whiteman, Ineka T.;Lim, Yun-An
氧化损伤与阿尔茨海默病和轻度认知障碍有关，但其与涉及淀粉样蛋白- β (A β)肽积累和过度磷酸化tau蛋白的神经病理病变发展的关系尚不清楚。我们发现，暴露于亚致死剂量的H(2)O(2)诱导初级鸡脑神经元氧化应激20小时后，总分泌内源性A β水平增加2.4倍。这是在细胞内淀粉样蛋白前体蛋白或tau蛋白水平没有变化的情况下发生的，而热休克蛋白90升高2.5倍。这些结果与衰老相关的氧化应激有助于阿尔茨海默病A β生成增加和分子伴侣上调的假设一致。
Oxidative damage is associated with Alzheimer's disease and mild cognitive impairment, but its relationship to the development of neuropathological lesions involving accumulation of amyloid-beta (A beta) peptides and hyperphosphorylated tau protein remains poorly understood. We show that inducing oxidative stress in primary chick brain neurons by exposure to sublethal doses of H(2)O(2) increases levels of total secreted endogenous A beta by 2.4-fold after 20 h. This occurs in the absence of changes to intracellular amyloid precursor protein or tau protein levels, while heat-shock protein 90 is elevated 2.5-fold. These results are consistent with the hypothesis that aging-associated oxidative stress contributes to increasing A beta generation and up-regulation of molecular chaperones in Alzheimer's disease.