β-Amyloid peptide-derived, oxygen-dependent free radicals inhibit glutamate uptake in cultured astrocytes: implications for Alzheimerʼs disease
| Autor: | N. W. Pedigo, Beverly J. Howard, P. Bummer, John M. Carney, L. Martin, Yaning Wang, D A Butterfield, K. Hensley, P. Cole, Marni E. Harris |
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| Rok vydání: | 1995 |
| Předmět: |
Amyloid beta-Peptides
Free Radicals Spin trapping Chemistry Circular Dichroism General Neuroscience Radical Neurotoxicity Glutamate receptor Glutamic Acid medicine.disease Rats Rats Sprague-Dawley medicine.anatomical_structure Biochemistry Alzheimer Disease Astrocytes medicine Animals Neurotoxin Neuroglia Neurotransmitter Uptake Inhibitors Senile plaques Cells Cultured Astrocyte |
| Zdroj: | NeuroReport. 6:1875-1879 |
| ISSN: | 0959-4965 |
| DOI: | 10.1097/00001756-199510020-00013 |
| Popis: | beta-Amyloid (A beta), the central constituent of senile plaques in Alzheimer's disease (AD) brains, was shown by us recently to generate free radicals in an oxygen dependent mechanism. A beta-derived free radicals were detected directly using electron paramagnetic resonance (EPR) spin trapping techniques employing the spin trap phenyl-alpha-tert-butylnitrone (PBN). We have extended these studies to investigate the nature of the oxyradicals derived from A beta peptides, and we show that these free radicals are able to inhibit glutamate uptake in cultured astrocytes. An implication of inhibited astrocyte glutamate uptake in brain is increased extracellular levels of glutamate, which is excitotoxic to neurons. These results support the hypothesis that A beta neurotoxicity in AD may be due in part to A beta-derived, oxygen-dependent free radical inhibition of glutamate uptake. |
| Databáze: | OpenAIRE |
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