Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents

This Article Full Text Full Text (PDF) PPT slides of all figures Supplemental Material Index Alert me when this article is cited Citation Map Services Email this article Similar articles in this journal Similar articles in PubMed Alert me to new content in the JEM Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Landau, A. M. Articles by Desbarats, J. Search for Related Content PubMed PubMed Citation Articles by Landau, A. M. Articles by Desbarats, J. Pubmed/NCBI databases Gene GEO Profiles HomoloGene OMIM UniGene Hazardous Substances DB 1-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE Medline Plus Health Information Parkinson's Disease Patient Rights Related Collections Related Article Social Bookmarking                      What's this?

¹ Department of Physiology, McGill University, Montreal, Quebec, Canada, H3G 1Y6
² Division of Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada, H3A 2B4
³ McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada, H3A 2B4
⁴ Guy-Bernier Research Center, Maisonneuve-Rosemont Hospital
⁵ Department of Medicine, University of Montreal, Montreal, Quebec, Canada, H1T 2M4

CORRESPONDENCE Julie Desbarats: Julie.desbarats{at}mcgill.ca

Fas (CD95), a member of the tumor necrosis factor-receptor superfamily, has been studied extensively as a death-inducing receptor in the immune system. However, Fas is also widely expressed in a number of other tissues, including in neurons. Here, we report that defects in the Fas/Fas ligand system unexpectedly render mice highly susceptible to neural degeneration in a model of Parkinson's disease. We found that Fas-deficient lymphoproliferative mice develop a dramatic phenotype resembling clinical Parkinson's disease, characterized by extensive nigrostriatal degeneration accompanied by tremor, hypokinesia, and loss of motor coordination, when treated with the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) at a dose that causes no neural degeneration or behavioral impairment in WT mice. Mice with generalized lymphoproliferative disease, which express a mutated Fas ligand, display an intermediate phenotype between that of lymphoproliferative and WT mice. Moreover, Fas engagement directly protects neuronal cells from MPTP/1-methyl-4-phenylpyridinium ion toxicity in vitro. Our data show that decreased Fas expression renders dopaminergic neurons highly susceptible to degeneration in response to a Parkinson-causing neurotoxin. These findings constitute the first evidence for a neuroprotective role for Fas in vivo.

CiteULike

Complore

Connotea

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

• Ruan, W., Lee, C. T., Desbarats, J. (2008). A Novel Juxtamembrane Domain in Tumor Necrosis Factor Receptor Superfamily Molecules Activates Rac1 and Controls Neurite Growth. Mol. Biol. Cell 19: 3192-3202 [Abstract] [Full Text]  
• Schumann, D. M., Maedler, K., Franklin, I., Konrad, D., Storling, J., Boni-Schnetzler, M., Gjinovci, A., Kurrer, M. O., Gauthier, B. R., Bosco, D., Andres, A., Berney, T., Greter, M., Becher, B., Chervonsky, A. V., Halban, P. A., Mandrup-Poulsen, T., Wollheim, C. B., Donath, M. Y. (2007). The Fas pathway is involved in pancreatic beta cell secretory function. Proc. Natl. Acad. Sci. USA 104: 2861-2866 [Abstract] [Full Text]  
• Landau, A. M., Luk, K. C., Jones, M.-L., Siegrist-Johnstone, R., Young, Y. K., Kouassi, E., Rymar, V. V., Dagher, A., Sadikot, A. F., Desbarats, J. (2005). Defective Fas expression exacerbates neurotoxicity in a model of Parkinson's disease. J. Cell Biol. 170: i11-i11 [Full Text]  

Home | Help | Feedback | Subscriptions | Archive | Search

TABLE OF CONTENTS