NR APMT
AU Turnbull,S.; Tabner,B.J.; Brown,D.R.; Allsop,D.
TI Quinacrine acts as an antioxidant and reduces the toxicity of the prion peptide PrP106-126
QU Neuroreport 2003 Sep 15; 14(13): 1743-5
PT journal article
AB The accumulation of protein aggregates in the brain is a central feature of several different neurodegenerative diseases. We have recently shown that Abeta and alpha-synuclein, associated with Alzheimer's disease, Parkinson's disease and related disorders, can both induce the formation of hydroxyl radicals following incubation in solution, upon addition of Fe(II). PrP106-126, a model peptide for the study of prion protein-mediated cell death, shares the same property. In this study we show that quinacrine (an anti-malarial drug and inhibitor of prion replication) acts as an effective antioxidant, readily scavenging hydroxyl radicals formed from hydrogen peroxide via the Fenton reaction or generated during incubation of the PrP106-126 peptide. Furthermore, the toxicity of PrP106-126 to cultured cells was significantly inhibited by quinacrine.
MH Animals; Antioxidants/*pharmacology; Cell Culture; Cerebellum/*drug effects; Electron Spin Resonance Spectroscopy; Enzyme Inhibitors/*pharmacology; Hydroxyl Radical/adverse effects/antagonists & inhibitors; Mice; Neurons/*drug effects; Prions/*drug effects/metabolism/toxicity; Quinacrine/*pharmacology; Support, Non-U.S. Gov't
AD Department of Biological Sciences, Lancaster University, Lancaster LA1 4YQ, UK
SP englisch
PO England