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

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.