title: Cross-linking cellular prion protein triggers neuronal apoptosis in vivo.
abstract: 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.
authors.affiliation: Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: Laura
authors.initials: L
authors.lastname: Solforosi
authors.forename: Jose R
authors.initials: JR
authors.lastname: Criado
authors.forename: Dorian B
authors.initials: DB
authors.lastname: McGavern
authors.forename: Sebastian
authors.initials: S
authors.lastname: Wirz
authors.forename: Manuel
authors.initials: M
authors.lastname: Sánchez-Alavez
authors.forename: Shuei
authors.initials: S
authors.lastname: Sugama
authors.forename: Lorraine A
authors.initials: LA
authors.lastname: DeGiorgio
authors.forename: Bruce T
authors.initials: BT
authors.lastname: Volpe
authors.forename: Erika
authors.initials: E
authors.lastname: Wiseman
authors.forename: Gil
authors.initials: G
authors.lastname: Abalos
authors.forename: Eliezer
authors.initials: E
authors.lastname: Masliah
authors.forename: Donald
authors.initials: D
authors.lastname: Gilden
authors.forename: Michael B
authors.initials: MB
authors.lastname: Oldstone
authors.forename: Bruno
authors.initials: B
authors.lastname: Conti
authors.forename: R Anthony
authors.initials: RA
authors.lastname: Williamson
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000378:metabolism*; D017209:Apoptosis; D002470:Cell Survival; D002531:Cerebellum / Q000166:cytology*; D003167:Complement Activation; D019281:Dimerization; D006624:Hippocampus / Q000166:cytology*; D007140:Immunoglobulin Fab Fragments / Q000276:immunology / Q000378:metabolism; D007074:Immunoglobulin G / Q000276:immunology / Q000378:metabolism; D020287:In Situ Nick-End Labeling; D051379:Mice; D008810:Mice, Inbred C57BL; D019006:Neural Cell Adhesion Molecules / Q000276:immunology / Q000378:metabolism; D009474:Neurons / Q000502:physiology*; D018621:PrPC Proteins / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D000911:Antibodies, Monoclonal; D007140:Immunoglobulin Fab Fragments; D007074:Immunoglobulin G; D019006:Neural Cell Adhesion Molecules; D018621:PrPC Proteins; D011994:Recombinant Proteins