NR AQDP
AU Solforosi,L.; Criado,J.R.; McGavern,D.B.; Wirz,S.; Sanchez-Alavez,M.; Sugama,S.; DeGiorgio,L.A.; Volpe,B.T.; Wiseman,E.; Abalos,G.C.; Masliah,E.; Gilden,D.; Oldstone,M.B.A.; Conti,B.; Williamson,R.A.
TI Cross-linking cellular prion protein triggers neuronal apoptosis in vivo
QU Science 2004 Mar 5; 303(5663): 1514-6
PT journal article
AB Neuronal death is a prominent, but poorly understood, pathological hallmark of prion disease. Notably, in the absence of the cellular prion protein (PrPc), the disease-associated isoform, PrPsc, appears not to be intrinsically neurotoxic, suggesting that PrPc itself may participate directly in the prion neurodegenerative cascade. Here, cross-linking PrPc in vivo with specific monoclonal antibodies was found to trigger rapid and extensive apoptosis in hippocampal and cerebellar neurons. These findings suggest that PrPc functions in the control of neuronal survival and provides a model to explore whether cross-linking of PrPc by oligomeric PrPsc can promote neuronal loss during prion infection.
MH Animals; Antibodies, Monoclonal/immunology/*metabolism; *Apoptosis; Cell Survival; Cerebellum/*cytology; Complement Activation; Dimerization; Hippocampus/*cytology; Immunoglobulin G/immunology/metabolism; Immunoglobulins, Fab/immunology/metabolism; In Situ Nick-End Labeling; Mice; Mice, Inbred C57BL; Neural Cell Adhesion Molecules/immunology/metabolism; Neurons/*physiology; PrPc Proteins/chemistry/immunology/*metabolism; Recombinant Proteins/metabolism; Signal Transduction; Support, Non-U.S. Gov't; Support, U.S. Gov't, Non-P.H.S.; Support, U.S. Gov't, P.H.S.
AD Laura Solforosi (lsolf@scripps.edu), Erika Wiseman, Gil Abalos, R. Anthony Williamson (anthony@scripps.edu), Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037, USA; Jose R. Criado, Dorian B. McGavern, Sebastian Wirz, Manuel Sánchez-Alavez, Shuei Sugama, Michael B. Oldstone, Bruno Conti, Department of Neuropharmacology, The Scripps Research Institute, La Jolla, CA 92037, USA; Sebastian Wirz, Shuei Sugama, Bruno Conti, The Harold Dorris Neurological Research Center, The Scripps Research Institute, La Jolla, CA 92037, USA; Lorraine A. DeGiorgio, Bruce T. Volpe, Department of Neurology and Neuroscience, The Burke Medical Research Institute, Weill Medical College of Cornell University, White Plains, NY 10605, USA; Eliezer Masliah, Departments of Neurosciences and Pathology, University of California San Diego, La Jolla, CA 92037, USA; Donald Gilden, Department of Neurology, University of Colorado, Denver, CO 80262, USA
SP englisch
PO USA