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Originally published in Science Express on 29 January 2004
Science 5 March 2004:
Vol. 303. no. 5663, pp. 1514 - 1516
DOI: 10.1126/science.1094273
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Reports

Cross-Linking Cellular Prion Protein Triggers Neuronal Apoptosis in Vivo

Laura Solforosi,1 Jose R. Criado,2 Dorian B. McGavern,2 Sebastian Wirz,2,3 Manuel Sánchez-Alavez,2 Shuei Sugama,2,3 Lorraine A. DeGiorgio,4 Bruce T. Volpe,4 Erika Wiseman,1 Gil Abalos,1 Eliezer Masliah,5 Donald Gilden,6 Michael B. Oldstone,2 Bruno Conti,2,3 R. Anthony Williamson1*

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.

1 Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037, USA.
2 Department of Neuropharmacology, The Scripps Research Institute, La Jolla, CA 92037, USA.
3 The Harold Dorris Neurological Research Center, The Scripps Research Institute, La Jolla, CA 92037, USA.
4 Department of Neurology and Neuroscience, The Burke Medical Research Institute, Weill Medical College of Cornell University, White Plains, NY 10605, USA.
5 Departments of Neurosciences and Pathology, University of California San Diego, La Jolla, CA 92037, USA.
6 Department of Neurology, University of Colorado, Denver, CO 80262, USA.

* To whom correspondence should be addressed. E-mail: anthony{at}scripps.edu

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