1. Astrocytic neurotoxicity: death receptor signalling in motoneuron disease

ALS is a devastating neurodegenerative disease characterized by the selective and gradual degeneration of motoneurons in the brain and spinal cord. There is growing evidence that a persistent inflammatory response contributes to ALS pathogenesis. The reactive astrocytes in the vicinity of motoneurons play a pivotal role by determining the extent of the inflammatory response from microglia and also by releasing factors selectively toxic for motoneurons.

1-1 astroschema-s


Death receptors can selectively trigger death of motoneurons. Mutant astrocytes can directly or indirectly contribute the activation of death pathway in motoneurons. Our main goals are to identify death signals emerging from reactive astrocytes, evaluate their potential as therapeutic candidates and determine their human relevance.

 

 

Our approaches rely on:

- Neuronal and non-neuronal primary cultures
- ES-derived motoneurons
- Microfluidic chambers
- Gene therapy and Immunotherapy
- Histopathology
- Neuromuscular junctions
- Motor behaviour

Major publications

Otsmane, B. et al., Neuroreport, 25(1):49-54, 2014
Bernard-Marissal, N. et al., J Neurosci, 30, 4901-12, 2012
Aebischer, J. et al.,Cell Death Diff, 18, 754-68, 2011
Mastroeni, R. et al., Ann Neurol, 66, 177-22, 2009
Raoul, C. et al., Proc Natl Acad Sci USA, 103, 6007-12, 2006
Raoul, C. et al., Nat Med, 11, 423-28, 2005
Raoul, C. et al., Neuron, 14:411-3, 2002

Collaborations

  • Patrick Aebischer (EPFL, Lausanne, Switzerland)
  • Brigitte Pettmann (Inmed, Marseille)
  • Linda Burkly (Cambridge, MA, USA)
  • Eric Kremer (IGMM, Montpellier)

 

Contact

Cédric Raoul