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 (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.
Della-Bianca
V
V
Department of Pathology, Section of General Pathology, University of Verona, Strada Le Grazie 8, Verona 37134, Italy.
Rossi
F
F
Armato
U
U
Dal-Pra
I
I
Costantini
C
C
Perini
G
G
Politi
V
V
Della Valle
G
G
D001665:Binding Sites; D015152:Blotting, Northern; D015153:Blotting, Western; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D008856:Microscopy, Fluorescence; D009447:Neuroblastoma / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism*; D011328:Prions / Q000378:metabolism*; D011485:Protein Binding; D020800:Receptor, Nerve Growth Factor; D017475:Receptors, Nerve Growth Factor / Q000737:chemistry* / Q000378:metabolism*; D019311:Staurosporine / Q000494:pharmacology; D013997:Time Factors; D014407:Tumor Cells, Cultured
D004791:Enzyme Inhibitors; D010446:Peptide Fragments; D011328:Prions; D020800:Receptor, Nerve Growth Factor; D017475:Receptors, Nerve Growth Factor; C082632:prion protein (106-126); C505530:CASP8 protein, human; C506433:CASP9 protein, human; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases; D019311:Staurosporine; D010100:Oxygen