Involvement of the 5-lipoxygenase pathway in the neurotoxicity of the prion peptide PrP106-126

Abstract

Transmissible spongiform encephalopathies are characterised by the transformation of the normal cellular prion protein (PrPC) into an abnormal isoform (PrPTSE). Previous studies have shown that N-methyl-D-aspartate (NMDA) receptor antagonists can inhibit glutathione depletion and neurotoxicity induced by PrPTSE and a toxic prion protein peptide, PrP106-126, in vitro. NMDA receptor activation is known to increase intracellular accumulation of Ca2+, resulting in up-regulation of arachidonic acid (AA) metabolism. This can stimulate the lipoxygenase pathways that may generate a number of potentially neurotoxic metabolites. Because of the putative relationship between AA breakdown and PrP106-126 ..