Cross-linking cellular prion protein triggers neuronal apoptosis in vivo.
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.
Solforosi
Laura
L
Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Criado
Jose R
JR
McGavern
Dorian B
DB
Wirz
Sebastian
S
Sánchez-Alavez
Manuel
M
Sugama
Shuei
S
DeGiorgio
Lorraine A
LA
Volpe
Bruce T
BT
Wiseman
Erika
E
Abalos
Gil
G
Masliah
Eliezer
E
Gilden
Donald
D
Oldstone
Michael B
MB
Conti
Bruno
B
Williamson
R Anthony
RA
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
D000911:Antibodies, Monoclonal; D007140:Immunoglobulin Fab Fragments; D007074:Immunoglobulin G; D019006:Neural Cell Adhesion Molecules; D018621:PrPC Proteins; D011994:Recombinant Proteins