Our project focuses on the analysis of the normal and pathological motor unit, with particular attention to the cellular and functional relationships between motor neurons, glial cells and muscle fiber. It links fundamental approaches of motor unit development and plasticity to the development of new therapeutic strategies in close collaboration with clinicians. The unique expertise developed within the team allows us to address these issues in connection with modulated muscular activity and physical exercise.
We are investigating motor unit alterations in two very severe human neurodegenerative diseases which lead to motor neuron death and for which no therapies are available currently, namely Spinal Muscular Atrophy (SMA) and Amyotrophic Lateral Sclerosis (ALS). Our ultimate objective is to identify mechanisms the activation of which can be modulated pharmacologically and which have therapeutic potential.
Our project is divided into three axes. The first deals with the study of neuromuscular development and plasticity during normal and pathological embryogenesis. One objective of this study is to identify the molecular mechanisms which control the muscle fiber phenotype, and which could be involved in the pathological aplasia and atrophy detected in ALS and SMA muscles. The second deals with the effects of physical exercise in mouse models of ALS and SMA that could help identify efficient neuroprotective mechanisms, notably for motor neurons, with an aim toward the design of exercise-based rehabilitation protocols for patients. The third objective is to establish the function of the SMN complex in the nucleus, in both the normal and SMA contexts and at identifying the mechanisms that regulate SMN accumulation and release at the Cajal Bodies (CB).
- Small-molecule flunarizine increases SMN protein in nuclear Cajal bodies and motor function in a mouse model of spinal muscular atrophy.
Sapaly D, Dos Santos M, Delers P, Biondi O, Quérol G, Houdebine L, Khoobarry K, Girardet F, Burlet P, Armand AS, Chanoine C, Bureau JF, Charbonnier F, Lefebvre S : Sci Rep, 2018
- Involvement of Aryl hydrocarbon receptor in myelination and in human nerve sheath tumorigenesis.
Shackleford G, Sampathkumar NK, Hichor M, Weill L, Meffre D, Juricek L, Laurendeau I, Chevallier A, Ortonne N, Larousserie F, Herbin M, Bièche I, Coumoul X, Beraneck M, Baulieu EE, Charbonnier F, Pasmant E, Massaad C : Proc Natl Acad Sci U S A, 2018
- Wnt proteins contribute to neuromuscular junction formation through distinct signaling pathways.
Messéant J, Ezan J, Delers P, Glebov K, Marchiol C, Lager F, Renault G, Tissir F, Montcouquiol M, Sans N, Legay C, Strochlic L : Development, 2017