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J. Biol. Chem. 276 (42): 38929-38933

© 2001 by The American Society for Biochemistry and Molecular Biology, Inc.

Neurotrophin p75 Receptor Is Involved in Neuronal Damage by Prion Peptide-(106–126)*

Vittorina Della-Bianca{ddagger}, Filippo Rossi{ddagger}§, Ubaldo Armato, Ilaria Dal-Pra, Claudio Costantini{ddagger}, Giovanni Perini||, Valeria Politi||, , and Giuliano Della Valle||

From the {ddagger}Department of Pathology, Section of General Pathology, University of Verona, Strada Le Grazie 8, Verona 37134, Italy, the Department of Biomedical and Surgical Sciences, Section of Histology and Embryology, University of Verona, Strada Le Grazie 8, Verona 37134, Italy, and the ||Department of Biology, University of Bologna, Via Selmi 3, Bologna 40126, Italy

ABSTRACT Back to Top

Abstract: In this work we have investigated the molecular basis of the neuronal damage induced by the prion peptide by searching for a surface receptor whose activation could be the first step of a cascade of events responsible for cell death. By using a human neuroblastoma cell line lacking all the neurotrophin receptors and derived clones expressing the full-length or truncated forms of the low affinity neurotrophin receptor (p75NTR), we have been able to demonstrate that the neuronal death induced by the prion protein fragment PrP-(106–126) is an active process mediated by a) the binding of the peptide to the extracellular region of p75NTR, b) the signaling function of the intracytoplasmic region of the receptor, and c) the activation of caspase-8 and the production of oxidant species.

Received for publication August 3, 2001.

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