Team "ALS : causes and mechanisms of motor neuron degeneration"

Scientific Teams

Team “ALS : causes and mechanisms of motor neuron degeneration”

Presentation

Main domain : Cellular & molecular neurosciences Subdomain : Clinical & translational neurosciences Séverine BOILLEE’s team investigates mechanisms of motor neuron (MN) degeneration in Amyotrophic Lateral Sclerosis (ALS or Lou Gehrig’s disease) resulting from pathological interactions between MNs and microglia/macrophages to find therapeutically promising pathways to slow disease progression through two main aims:

To understand how known/new ALS genes, identified using dedicated genetic approaches, lead to MN death and deregulated microglial responses, with the goal to identify and functionally validate common/divergent pathological pathways, using iPSc-derived MNs/microglia, mouse models and human post-mortem tissues
Focusing on the unique characteristics of spinal MNs, to assess impact and ALS disease modifying capacities of peripheral nerve macrophages (vs CNS microglia), using gene profiling in ALS mice and patient’s blood- and iPSc-derived microglia/macrophages. The final goal being to find disease modifying targets at the periphery, therapeutically easier to reach than in the CNS.

Major publications

Chiot A., Zaïdi S., Iltis C., Ribon M., Berriat F., Schiaffino L., Jolly A., de la Grange P., Mallat M., Bohl D., Millecamps S., Seilhean D., Lobsiger C.S., Boillée S. Modifying macrophages at the periphery has the capacity to change microglial reactivity and toextend ALS survival. Nat Neurosci. In press.
Amador M.d.M., Muratet F., Teyssou E., Banneau G., Danel-Brunaud V., Allart E., Antoine J.-C., Camdessanché J.-P., Anheim M., Rudolf G., Tranchant C., Fleury M.-C., Bernard E., Stevanin G. & Millecamps S. Spastic paraplegia due to recessive or dominant mutations in ERLIN2 can convert to ALS, Neurology: Genetics, 5 (6):e374 (2019).
Teyssou E.*, Chartier L.*, Amador M.d.M., Lam R., Lautrette G., Nicol M., Machat S., Da Barroca S., Moigneu C., Mairey M., Larmonier T., Saker S., Dussert C., Forlani S., Fontaine B., Seilhean D., Bohl D., Boillée S., Meininger V., Couratier P., Salachas F., Stevanin G., Millecamps S. Novel UBQLN2 mutations linked to Amyotrophic Lateral Sclerosis and atypical Hereditary Spastic Paraplegia phenotype through defective HSP70- mediated proteolysis. Neurobiology of Aging, 58:239.e11-239.e20. (2017).
*equal contribution.
Mesci P., Zaïdi S., Lobsiger C.S., Millecamps S., Escartin C., Seilhean D., Sato H., Mallat M. & Boillée S. System xC- is a mediator of microglial function and its deletion slows symptoms in ALS mice. Brain, 138(Pt 1):53-68 (2015).
Toli D., Buttigieg D., Blanchard S., Lemonnier T., Lamotte d’Incamps B., Bellouze S., Baillat G., Bohl D.*, Haase G.* Modeling amyotrophic lateral sclerosis in pure human iPSc-derived motor neurons isolated by a novel FACS double selection technique. Neurobiol. D