Phospholipids influence the aggregation of recombinant ovine prions. From rapid extensive aggregation to amyloidogenic conversion

Biochimica Et Biophysica Acta
Kirill TsiroulnikovThomas Haertlé

Abstract

The transformation of prion protein (PrP) into its insoluble amyloid form correlates with neurodegeneration in transmissible spongiform encephalopathies. PrP is connected to the neuronal membrane by a covalently-linked glycosylphosphatidylinositol (GPI) anchor. The current study demonstrates that phosphatidylinositol and phosphatidylethanolamine in low concentrations (0.5-50 muM) stimulate rapid unlimited aggregation of PrP. At a higher concentration (500 muM), lipid particles prevent the formation of large PrP aggregates and induce an increase in the beta-sheet structure content of PrP protein. Thus, the liberation of PrP from the membrane and its direct interaction with its own GPI moiety, as well as with membrane lipids, can promote the formation of aggregated structures of PrP. The phospholipids studied are also able to upregulate the aggregation of oligomeric PrP forms (12-mers and 36-mers), the neurotoxicity of which has been reported recently. Low phosphatidylinositol concentrations induce these oligomers to form aggregates of smaller size when compared with aggregates formed directly from monomers. The inhibition of extensive aggregation observed at a high concentration of phosphatidylinositol (500 muM) results in both ...Continue Reading

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Citations

Sep 6, 2013·International Journal of Molecular Sciences·Shen-Jie LinCheng-I Lee
Jun 22, 2011·Biochimica Et Biophysica Acta·Yulia Y StroylovaThomas Haertlé
Mar 2, 2010·International Journal of Pharmaceutics·Wei WangDirk Teagarden
Jun 17, 2010·Journal of Peptide Science : an Official Publication of the European Peptide Society·Sabina SonkinaJosep Cladera
Jul 12, 2012·Archives of Biochemistry and Biophysics·Yulia Y StroylovaThomas Haertlé
Aug 3, 2017·Journal of Lipid Research·Véronique PerrierCatherine Desrumaux
Feb 19, 2021·Chemistry and Physics of Lipids·Michael OverduinDavid Westaway
Jul 6, 2021·Frontiers in Neuroscience·Juliana N AngelliTuane C R G Vieira

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