Davis D R, Anderton B H, Brion J P, Reynolds C H, Hanger D P
Department of Neuroscience, Institute of Psychiarry, London, England.
J Neurochem. 1997 Apr;68(4):1590-7. doi: 10.1046/j.1471-4159.1997.68041590.x.
Oxidative stress and free radical damage have been implicated in the neurodegenerative changes characteristic of several neurodegenerative diseases, including Alzheimer's disease. There is experimental evidence that the neurotoxicity of beta-amyloid is mediated via free radicals, and as the deposition of beta-amyloid apparently precedes the formation of paired helical filaments (PHF) in Alzheimer's disease, we have investigated whether subjecting primary neuronal cultures to oxidative stress induces changes in the phosphorylation state of the principal PHF protein tau that resemble those found in PHF-tau. Contrary to causing an increase in tau phosphorylation, treatment of neurones with hydrogen peroxide caused a dephosphorylation of tau and so we conclude that oxidative stress is not the direct cause of tau hyperphosphorylation and hence of PHF formation.
氧化应激和自由基损伤与包括阿尔茨海默病在内的几种神经退行性疾病的神经退行性变化有关。有实验证据表明，β-淀粉样蛋白的神经毒性是通过自由基介导的，并且由于β-淀粉样蛋白的沉积显然先于阿尔茨海默病中双螺旋丝（PHF）的形成，我们研究了使原代神经元培养物遭受氧化应激是否会诱导主要PHF蛋白tau的磷酸化状态发生变化，这些变化类似于在PHF-tau中发现的变化。与导致tau磷酸化增加相反，用过氧化氢处理神经元导致tau去磷酸化，因此我们得出结论，氧化应激不是tau过度磷酸化的直接原因，因此也不是PHF形成的直接原因。
