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Fas expression promotes proteasomal activity in toxin-induced parkinsonism

Published online by Cambridge University Press:  24 June 2014

Anne M. Landau ,
Rosmarie Siegrist-Johnstone  and
Julie Desbarats
Anne M. Landau*
Affiliation:
Department of Physiology, McGill University, Montreal, Quebec, H3G 1Y6, Canada Department of Nuclear Medicine, PET Center and Center of Functionally Integrative Neuroscience, Aarhus University Hospital, Aarhus, Denmark
Rosmarie Siegrist-Johnstone
Affiliation:
Department of Physiology, McGill University, Montreal, Quebec, H3G 1Y6, Canada
Julie Desbarats
Affiliation:
Department of Physiology, McGill University, Montreal, Quebec, H3G 1Y6, Canada
*
Anne M. Landau, Department of Nuclear Medicine, PET Center and Center of Functionally Integrative Neuroscience, Aarhus University Hospital, Norrebrogade 44, Building 10G, 8000 Aarhus C, Denmark. Tel: +45 8949 4378; Fax: +45 8949 3020; E-mail: [email protected]
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Extract

Objective: Fas (CD95), commonly categorised as a death receptor due to its well-defined role in apoptosis, can paradoxically also promote neuroprotection. We have previously found that defects in Fas signalling render mice highly susceptible to neural degeneration in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson's disease (PD). Decreased activity of the ubiquitin proteasome system and accumulation of protein aggregates are implicated in PD pathogenesis. Here, we investigate the relationship between Fas and ubiquitin proteasomal activity in neuronal cells.

Methods: We performed proteasome assays in neuroblastoma cells and in midbrain cultures of wild-type and Fas-deficient mice.

Results: Neuroblastoma cells upregulated proteasomal activity in response to an activating Fas antibody in vitro. Furthermore, neural tissue from Fas-deficient mice showed decreased proteasomal activity compared with the tissue from wild-type mice when exposed to a PD-inducing toxin in vivo.

Conclusion: These findings suggest that mechanisms for Fas-mediated neuroprotection may include Fas-induced upregulation of proteasomal activity, and consequently less accumulation of toxic protein aggregates.

Keywords

CD951-methyl-4-phenyl-1,2,3,6-tetrahydropyridineParkinson's diseaseubiquitin
Type
Research Article
Information
Acta Neuropsychiatrica , Volume 24 , Issue 3 , June 2012 , pp. 166 - 171
Copyright
Copyright © Cambridge University Press 2011

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