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Originally published In Press as doi:10.1074/jbc.M107454200 on August 6, 2001

J. Biol. Chem., Vol. 276, Issue 42, 38929-38933, October 19, 2001
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Neurotrophin p75 Receptor Is Involved in Neuronal Damage by Prion Peptide-(106-126)*

Vittorina Della-BiancaDagger , Filippo RossiDagger §, Ubaldo Armato, Ilaria Dal-Pra, Claudio CostantiniDagger , Giovanni Perini||, Valeria Politi||, and Giuliano Della Valle||

From the Dagger  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

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.

* This work was supported by grants from Progetto Sanità 1996-97, Fondazione Cariverona (to F. R. and U. A.), Cofinanziamento Ministero dell'Università e della Ricerca Scientifica e Tecnologica-Università (to F. R. and U. A.), and from 5th Framework Program of the European Union Grant NOQLRT-1999-00573 (to G. D. V.).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

§ To whom correspondence should be addressed. Tel.: 39-045-8027121; Fax: 39-045-8027127; E-mail: Filippo.Rossi@univr.it.

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