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The Journal of Neuroscience, November 21, 2007, 27(47):13022-13027; doi:10.1523/JNEUROSCI.3290-07.2007

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Brief Communications
Diminishing Apoptosis by Deletion of Bax or Overexpression of Bcl-2 Does Not Protect against Infectious Prion Toxicity In Vivo

Andrew D. Steele,¹ Oliver D. King,¹ Walker S. Jackson,¹ Claudio A. Hetz,^2,3 Andrew W. Borkowski,¹ Peter Thielen,² Robert Wollmann,⁴ and Susan Lindquist¹

¹Whitehead Institute for Biomedical Research, Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, ²Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts 02115, ³Department of Cellular and Molecular Biology, Institute of Biomedical Sciences, Fondo Nacional Areas Prioritas Center for Molecular Studies of the Cell, University of Chile, Santiago, Chile, and ⁴Department of Pathology, University of Chicago, Chicago, Illinois 60637

Correspondence should be addressed to Susan Lindquist, Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142. Email: Lindquist_admin{at}wi.mit.edu

B-cell lymphoma protein 2 (Bcl-2) and Bcl-2-associated X protein (Bax), key antiapoptotic and proapoptotic proteins, respectively, have important roles in acute and chronic models of neurologic disease. Several studies have implicated Bax and Bcl-2 in mediating neurotoxicity in prion diseases. To determine whether diminishing apoptotic cell death is protective in an infectious prion disease model we inoculated mice that either were null for proapoptotic Bax or overexpressed antiapoptotic Bcl-2. Interestingly, genetic manipulation of apoptosis did not lessen the clinical severity of disease. Moreover, some disease parameters, such as behavioral alterations and death, occurred slightly earlier in mice that are null for Bax or overexpress Bcl-2. These results suggest that Bax and Bcl-2 mediated apoptotic pathways are not the major contributing factor to the clinical or pathological features of infectious prion disease.

Key words: PrP; home cage; amyloid; cell death; necrosis; transmissible

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Received July 19, 2007; revised Sept. 11, 2007; accepted Oct. 13, 2007.

Correspondence should be addressed to Susan Lindquist, Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142. Email: Lindquist_admin{at}wi.mit.edu

This article has been cited by other articles:

				A. D. Steele All quiet on the neuronal front: NMDA receptor inhibition by prion protein J. Cell Biol., May 1, 2008; 181(3): 407 - 409. [Abstract] [Full Text] [PDF]

				C. Hetz, A.-H. Lee, D. Gonzalez-Romero, P. Thielen, J. Castilla, C. Soto, and L. H. Glimcher Unfolded protein response transcription factor XBP-1 does not influence prion replication or pathogenesis PNAS, January 15, 2008; 105(2): 757 - 762. [Abstract] [Full Text] [PDF]

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