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A glycosylphosphatidylinositol analogue reduced prion-derived peptide mediated activation of cytoplasmic phospholipase A2, synapse degeneration and neuronal death.

Bate, C, Tayebi, M and Williams, A (2010) A glycosylphosphatidylinositol analogue reduced prion-derived peptide mediated activation of cytoplasmic phospholipase A2, synapse degeneration and neuronal death. Neuropharmacology, 59 (1-2). pp. 93-99.

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Abstract

The pathogenesis of prion diseases includes synapse degeneration and neuronal death. Here we report that pre-treatment with glucosamine-phosphatidylinositol (glucosamine-PI), a synthetic analogue of the glycosylphosphatidylinositol (GPI) anchor that attaches the prion protein (PrP(C)) to plasma membranes, increased the resistance of cultured cortical neurones to the toxic effects of the prion-derived peptide PrP82-146. Pre-treatment with glucosamine-PI reduced the PrP82-146 induced activation of cytoplasmic phospholipase A(2) (cPLA(2)), activation of caspase-3 and synapse degeneration. The addition of glucosamine-PI significantly increased the amount of cholesterol within neuronal membranes consistent with the hypothesis that GPI anchors sequester cholesterol. Whereas in untreated neurones PrP82-146 was found within lipid rafts, in glucosamine-PI treated neurones most PrP82-146 was found in the normal cell membrane and was rerouted into the lysosomes. Complex GPI anchors isolated from PrP(C), Thy-1 or CD55 were also protective against PrP82-146. We conclude that glucosamine-PI, or isolated GPI anchors, can modify local membrane micro-environments that are important in the initiation of signalling events that mediate PrP82-146 induced neurodegeneration.

Item Type: Article
Authors :
NameEmailORCID
Bate, CUNSPECIFIEDUNSPECIFIED
Tayebi, Mm.tayebi@surrey.ac.ukUNSPECIFIED
Williams, AUNSPECIFIEDUNSPECIFIED
Date : July 2010
Identification Number : https://doi.org/10.1016/j.neuropharm.2010.04.002
Uncontrolled Keywords : Animals, Antigens, CD55, Antigens, Thy-1, Cell Membrane, Cells, Cultured, Central Nervous System Agents, Cerebral Cortex, Cholesterol, Cytoplasm, Glycosylphosphatidylinositols, Lysosomes, Mice, Nerve Degeneration, Neurons, Peptides, Phosphatidylinositols, Phospholipases A2, PrPC Proteins, Synapses
Related URLs :
Depositing User : Symplectic Elements
Date Deposited : 17 May 2017 10:09
Last Modified : 17 May 2017 14:47
URI: http://epubs.surrey.ac.uk/id/eprint/826637

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