NR ADFT
AU Della-Bianca,V.; Rossi,F.; Armato,U.; Dal-Pra,I.; Costantini,C.; Perini,G.; Politi,V.; Della Valle,G.
TI Neurotrophin p75 receptor is involved in neuronal damage by prion peptide-(106-126)
QU The Journal of Biological Chemistry 2001 Oct 19; 276(42): 38929-33
PT journal article
AB 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 (p75(NTR)), 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 p75(NTR), b) the signaling function of the intracytoplasmic region of the receptor, and c) the activation of caspase-8 and the production of oxidant species.
MH Binding Sites; Blotting, Northern; Blotting, Western; Caspases/metabolism; Dose-Response Relationship, Drug; Enzyme Activation; Enzyme Inhibitors/pharmacology; Human; Microscopy, Fluorescence; Neuroblastoma/metabolism; Neurons/*metabolism; Oxygen/metabolism; Peptide Fragments/*metabolism; Prions/*metabolism; Protein Binding; Receptors, Nerve Growth Factor/*chemistry/*metabolism; Staurosporine/pharmacology; Support, Non-U.S. Gov't; Time Factors; Tumor Cells, Cultured
AD Department of Pathology, Section of General Pathology, University of Verona, Strada Le Grazie 8, Verona 37134, Italy.
SP englisch
PO USA