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 damag e induced by the prion peptide by searching for a surface receptor whose ac tivation could be the first step of a cascade of events responsible for cel l death. By using a human neuroblastoma cell line lacking all the neurotrop hin receptors and derived clones expressing the full-length or truncated fo rms of the low affinity neurotrophin receptor (p75(NTR)), we have been able to demonstrate that the neuronal death induced by the prion protein fragme nt PrP-(106-126) is an active process mediated by a) the binding of the pep tide to the extracellular region of p75(NTR), b) the signaling function of the intracytoplasmic region of the receptor, and c) the activation of caspa se-8 and the production of oxidant species.