Kumar U, Dunlop D M, Richardson J S
Department of Pharmacology, College of Medicine, University of Saskatchewan, Saskatoon, Canada.
Int J Neurosci. 1994 Dec;79(3-4):185-90. doi: 10.3109/00207459408986079.
The neuropathological characteristics of Alzheimer's disease include the selective loss of neurons and the development of senile plaques and neurofibrillary tangles. These plaques and tangles are invariably associated with deposits of an insoluble protein, beta-amyloid, and the hypothesis that the beta-amyloid is responsible for the neuronal loss in Alzheimer's disease has received considerable support. The neurotoxic action of beta-amyloid has been demonstrated in primary cultures of cortical and hippocampal neurons and in PC-12 cells. The present study reports that the neurotoxicity of beta-amyloid is reduced by the antioxidant drug U-78517F. On the basis of this observation, we suggest that the neurotoxic effect of beta-amyloid is mediated by oxygen free radicals. The clinical use of antioxidant interventions may reduce neurodegeneration and the progression of the symptoms in patients with Alzheimer's disease.
阿尔茨海默病的神经病理学特征包括神经元的选择性丧失以及老年斑和神经原纤维缠结的形成。这些斑块和缠结总是与一种不溶性蛋白质β-淀粉样蛋白的沉积相关，并且β-淀粉样蛋白导致阿尔茨海默病中神经元丧失的假说得到了相当多的支持。β-淀粉样蛋白的神经毒性作用已在皮质和海马神经元的原代培养物以及PC-12细胞中得到证实。本研究报告称，抗氧化药物U-78517F可降低β-淀粉样蛋白的神经毒性。基于这一观察结果，我们认为β-淀粉样蛋白的神经毒性作用是由氧自由基介导的。抗氧化干预措施的临床应用可能会减少阿尔茨海默病患者的神经退行性变和症状进展。
