The pathological prion protein forms ionic conductance in lipid bilayer |
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Authors: | Paulis Daniele Maras Bruno Schininà M Eugenia di Francesco Laura Principe Serena Galeno Roberta Abdel-Haq Hanin Cardone Franco Florio Tullio Pocchiari Maurizio Mazzanti Michele |
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Affiliation: | a Dipartimento di Scienze Biomolecolari e Biotecnologie, University of Milan, Italy b Dipartimento di Scienze Biochimiche, “Sapienza” University of Rome, Italy c Dipartimento di Biologia Cellulare e Neuroscienze, Istituto Superiore di Sanità, Rome, Italy d Laboratorio di Farmacologia, Dipartimento di Oncologia, Biologia e Genetica & Centro di Eccellenza per la Ricerca Biomedica (CEBR), University of Genova, Genova, Italy |
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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 (PrPTSE). PrPTSE pre-amyloid fibrils are supposed to induce neurodegenerative lesions possibly through the alteration of membrane permeability. The effect of PrPTSE on cellular membranes has been modeled in vitro by synthetic peptides that are, however, only partially representative of PrPTSE 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. |
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Keywords: | CNS, central nervous system TSEs, transmissible spongiform encephalopathies PrPTSE, pathologic isoform of the prion protein PrPC, physiologic isoform of the prion protein PrP27-30, protease resistant core of pathologic PrP |
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