The acute neurotoxic effect of beta-amyloid on mature cultures of rat hippocampal neurons is attenuated by the anti-oxidant U-78517F.
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.
Kumar
U
U
Department of Pharmacology, College of Medicine, University of Saskatchewan, Saskatoon, Canada.
Dunlop
D M
DM
Richardson
J S
JS
D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002478:Cells, Cultured; D016922:Cellular Senescence; D002839:Chromans / Q000494:pharmacology*; D016166:Free Radical Scavengers / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects*; D009498:Neurotoxins / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D016229:Amyloid beta-Peptides; D000975:Antioxidants; D002839:Chromans; D016166:Free Radical Scavengers; D009498:Neurotoxins; D010879:Piperazines; C066382:U 78517F