title: The pathological prion protein forms ionic conductance in lipid bilayer.
abstract: Transmissible spongiform encephalopathies (TSEs) are neurodegenerative pathologies characterized by the accumulation of amyloid fibrils mainly composed of the pathological isoform of the prion protein (PrP(TSE)). PrP(TSE) pre-amyloid fibrils are supposed to induce neurodegenerative lesions possibly through the alteration of membrane permeability. The effect of PrP(TSE) on cellular membranes has been modeled in vitro by synthetic peptides that are, however, only partially representative of PrP(TSE) isoforms found in vivo. In the present work we show that a synthetic membrane exposed to PrP27-30 extracted from TSE-infected hamster brains changes its permeability because of the formation of molecular pores that alter the conductance of the synthetic lipid bilayer. Synthetic membrane challenged with the recombinant prion peptide PrP90-231 shows a much lower conductance. Elevation of calcium ion concentration not only increases the current amplitude due to the action of both PrP27-30 and PrP90-231 on the membrane, but also amplifies the interaction of PrP90-231 with the lipid bilayer.
authors.affiliation: Dipartimento di Scienze Biomolecolari e Biotecnologie, University of Milan, Italy.
authors.forename: Daniele
authors.initials: D
authors.lastname: Paulis
authors.forename: Bruno
authors.initials: B
authors.lastname: Maras
authors.forename: M Eugenia
authors.initials: ME
authors.lastname: Schininà
authors.forename: Laura
authors.initials: L
authors.lastname: di Francesco
authors.forename: Serena
authors.initials: S
authors.lastname: Principe
authors.forename: Roberta
authors.initials: R
authors.lastname: Galeno
authors.forename: Hanin
authors.initials: H
authors.lastname: Abdel-Haq
authors.forename: Franco
authors.initials: F
authors.lastname: Cardone
authors.forename: Tullio
authors.initials: T
authors.lastname: Florio
authors.forename: Maurizio
authors.initials: M
authors.lastname: Pocchiari
authors.forename: Michele
authors.initials: M
authors.lastname: Mazzanti
mesh_terms: D000818:Animals; D006224:Cricetinae; D017136:Ion Transport; D008051:Lipid Bilayers; D008647:Mesocricetus; D011328:Prions / Q000502:physiology*
chemical_list: D008051:Lipid Bilayers; D011328:Prions