Neuropharmacology, 2010-07, Vol.59 (1-2), p.93-99
2010
Details
- Autor(en) / Beteiligte
- Titel
- A glycosylphosphatidylinositol analogue reduced prion-derived peptide mediated activation of cytoplasmic phospholipase A2, synapse degeneration and neuronal death
- Ist Teil von
- Neuropharmacology, 2010-07, Vol.59 (1-2), p.93-99
- Ort / Verlag
- England
- Erscheinungsjahr
- 2010
- Link zum Volltext
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0028-3908eISSN: 1873-7064DOI: 10.1016/j.neuropharm.2010.04.002Titel-ID: cdi_crossref_primary_10_1016_j_neuropharm_2010_04_002
- Format
- –
- Schlagworte
- Animals, CD55 Antigens - metabolism, Cell Membrane - drug effects, Cell Membrane - physiology, Cells, Cultured, Central Nervous System Agents - pharmacology, Cerebral Cortex - drug effects, Cerebral Cortex - physiology, Cholesterol - metabolism, Cytoplasm - drug effects, Cytoplasm - physiology, Glycosylphosphatidylinositols - metabolism, Lysosomes - drug effects, Lysosomes - physiology, Mice, Nerve Degeneration - drug therapy, Nerve Degeneration - metabolism, Neurons - drug effects, Neurons - physiology, Peptides - metabolism, Phosphatidylinositols - pharmacology, Phospholipases A2 - metabolism, PrPC Proteins - metabolism, Synapses - drug effects, Synapses - physiology, Thy-1 Antigens - metabolism