In vertebrate, axons are insulated by myelin sheaths which enable the rapid saltatory propagation of the action potentials and provide them with a metabolic support. The myelin is formed by glial cells: Schwann cells in peripheral nervous system and oligodendrocytes in central nervous system. In several human pathologies, either the structure or the physiology of myelinated axons is altered leading to axonal defects, conduction slowing or conduction loss.
We aim to 1) understand how the glial cells contribute to the metabolic support of myelinated axons in health and disease.
2) to develop new therapeutic strategies for demyelinating and axonal disorders.
How glial cells provide their metabolic support to axons in not clear. Several data indicate they supply lactate to the axon which can be converted into pyruvate to maintain substrates for the electron transport chain in order to produce cellular energy in the form of ATP. How important lactate is to a healthy or damaged axon is not understood. Using live imaging approaches, we study the role of glial derived lactate in myelinated and demyelinated axons, particularly in the production of ATP and axonal maintenance
The most frequent inherited neuropathy is a demyelinating disease resulting from the loss of the myelin sheath. We are developing a pharmacological approach to prevent peripheral demyelination.
Charcot-Marie-Tooth diseases (CMTs) are a group of hereditary peripheral neuropathies defined by distal muscle weakness, atrophy and sensory loss. There is no cure for CMTs but one approach for a treatment is gene therapy. Our goal is to provide a proof of principle for gene therapy in peripheral nerves using adeno-associated viral vector (AAV).
Inflammatory neuropathies are heterogeneous autoimmune pathologies that affect peripheral nerves. Our groups have shown that nodes of Ranvier can be the targets of the immune attack in inflammatory neuropathies. Our goal is to identify the pathogenic mechanisms leading to conduction loss in human demyelinating pathologies, identify novel diagnostic biomarkers, and determine the function of myelin proteins.