NR AOZG
AU Solforosi,L.; Criado,J.R.; Wirz,S.; McGavern,D.B.; Sanchez,M.; Wiseman,E.; Abalos,G.C.; Conti,B.; Williamson,R.A.
TI Neuronal apoptosis in vivo triggered by PrPc-specific antibody
QU International Conference - Prion diseases: from basic research to intervention concepts - TSE-Forum, 08.10.-10.10.2003, Gasteig, München - Poster session - PG-12
PT Konferenz-Poster
AB Neuronal loss is a prominent feature of prion pathogenesis. However, the molecular events promoting neuronal dysfunction and neurodegeneration remain poorly understood. Earlier studies of prions in mice have clearly identified that damage is not inflicted upon tissues that do not express PrPc. Moreover, antibody-mediated cross-linking of PrPc on cultured cells has been associated with the activation of signal transduction pathways. Here, we have studied the effect of antibody binding to PrPc in vivo. Stereotaxic injection of purified PrPc-reactive monoclonal antibodies into the cortex of Prnp+/+ mouse brain lead to the widespread loss of hippocampal neurons via apoptosis within 24 hours. No tissue damage resulted following injection of control antibody, or injection of PrPc-specific antibody into the brains of Prnpo/o mice. We conclude that induction of neuronal apoptosis via binding to PrPc may play a significant role in neurodegeneration caused by prions.
AD Laura Solforosi (lsolf@scripps.edu), Erika Wiseman, Gil C. Abalos, R. Anthony Williamson (anthony@scripps.edu), Department of Immunology, Scripps Research Institute, La Jolla, CA 92037, USA; Jose R. Criado(jcriado@scripps.edu), Sebastian Wirz, Dorian B. McGavern, M. Sanchez, Bruno Conti, Department of Neuropharmacology, Scripps Research Institute, USA
SP englisch
PO Deutschland