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Cédric Raoul"Motoneuron pathology: death signalling and therapeutic perspectives".

Abstract :


Motoneuron diseases (MND) encompass a group of devastating neurodegenerative disorders characterised by the progressive and selective death of motoneurons in the spinal cord, brainstem and/or cerebral cortex.
Amyotrophic Lateral Sclerosis (ALS), the most common MND, initiates in mid-life by muscle wasting, progressing rapidly to a generalized paralysis that leads irrevocably to death within 2 or 5 years of clinical onset. ALS has a complex multifactorial aetiology as reflected by the large predominance of sporadic forms of the disease (90%). The discovery of mutations in the SOD1 gene in some familial ALS cases and the development of mutant SOD1 mouse models have greatly contributed to our understanding of ALS. Nevertheless, there is presently no efficient treatment for this fatal neurodegenerative disease.
Our main research focus is to determine which death pathways are common to familial and sporadic ALS to allow for the development of pertinent therapeutic approaches. More precisely, we develop and study different ALS-relevant experimental models in order to understand how death receptor pathways, protein aggregation and organelle-specific death signals converge to the selective loss of motoneurons. Ultimately, our goal is to develop viral-based gene therapy approaches to target common signalling mechanisms.

Selected publications

Collapsin response mediator protein 4a (CRMP4a) is upregulated in motoneurons of mutant SOD1 mice and can trigger motoneuron axonal degeneration and cell death.Duplan L, Bernard N, Casseron W, Dudley K, Thouvenot E, Honnorat J, Rogemond V, De Bovis B, Aebischer P, Marin P, Raoul C, Henderson CE, Pettmann B.J Neurosci. 2010 Jan 13;30(2):785-96.
Raoul C, Buhler E, Sadeghi C, Jacquier A, Aebischer P, Pettmann B, Henderson CE, Haase G, (2006) Chronic activation in presymptomatic amyotrophic lateral sclerosis (ALS) mice of a feedback loop involving Fas, Daxx, and FasL (Proc Natl Acad Sci U S A.)
Raoul C, Abbas-Terki T, Bensadoun JC, Guillot S, Haase G, Szulc J, Henderson CE, Aebischer P, (2005) Lentiviral-mediated silencing of SOD1 through RNA interference retards disease onset and progression in a mouse model of ALS (Nat Med.)

Gwendal Le Masson