title: Fas expression promotes proteasomal activity in toxin-induced parkinsonism.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Physiology, McGill University, Montreal, Quebec, H3G 1Y6, Canada.
authors.forename: Anne M
authors.initials: AM
authors.lastname: Landau
authors.affiliation: Department of Physiology, McGill University, Montreal, Quebec, H3G 1Y6, Canada.
authors.forename: Rosmarie
authors.initials: R
authors.lastname: Siegrist-Johnstone
authors.affiliation: Department of Physiology, McGill University, Montreal, Quebec, H3G 1Y6, Canada.
authors.forename: Julie
authors.initials: J
authors.lastname: Desbarats