NR AQOL
AU Sassoon,J.; Daniels,M.; Brown,D.R.
TI Astrocytic regulation of NMDA receptor subunit composition modulates the toxicity of prion peptide PrP106-126
QU Molecular and Cellular Neurosciences 2004 Jan; 25(1): 181-91
PT journal article
AB Prion diseases are neurodegenerative conditions. The main pathological alterations common to these diseases include the loss of neurones, gliosis and the deposition of an abnormal isoform of the prion protein in aggregates in the nervous tissue. Prevention of the devastating effects of prion disease requires prevention of neuronal death. Therefore, understanding the mechanism by which this occurs is essential. Cell culture studies using the synthetic peptide PrP106-126 have been central to developing a model of this mechanism. Using a coculture system, we have shown that PrP106-126 caused neuronal death mediated by glutamate. This neuronal death resulted from modification of the expression of NMDA receptor subtypes stimulated by the exposure of neurones to the combination of astrocytic factors, elevated Cu and PrP106-126. The results of these experiments suggest neuronal death in prion disease might be reduced by the use of NMDA receptor antagonists such as MK801 or inhibitors of the arachidonic acid metabolism pathway.
MH Animals; Animals, Newborn; Arachidonic Acid/antagonists & inhibitors/metabolism; Astrocytes/metabolism/*secretion; Cell Communication/physiology; Cells, Cultured; Coculture; Copper/metabolism; Excitatory Amino Acid Antagonists/pharmacology/therapeutic use; Glutamic Acid/metabolism; Nerve Degeneration/chemically induced/*metabolism/physiopathology; Neurons/drug effects/*metabolism/pathology; Peptide Fragments/metabolism/*toxicity; Prion Diseases/drug therapy/*metabolism/physiopathology; Prions/metabolism/*toxicity; Protein Subunits/drug effects/metabolism; Rats; Rats, Sprague-Dawley; Receptors, N-Methyl-D-Aspartate/drug effects/*metabolism; Support, Non-U.S. Gov't
AD Department of Biology and Biochemistry, University of Bath, Bath BA2 7AY, UK
SP englisch
PO USA