iPSc

Causes de la SLA et mécanismes de la dégénérescence motoneuronale

Domaine de recherche principal: 

Neurological and psychiatric diseases

Mots clefs: 

Amyotrophic Lateral Sclerosis (ALS)
genetics
motor neurons degeneration
neuroimmunology
iPSc

Labelisation ENP: 

2016

Centre de recherche / Institut: 

Institut du Cerveau et de la Moelle épinière
https://icm-institute.org/fr/equipe-scientifiques/?team-keyword=&leader-id%5B%5D...

Code unité de recherche: 

UMRS 1127 UMR 7225

Amyotrophic Lateral Sclerosis (ALS) is the most common adult-onset motor neuron disease. Although mostly sporadic, major geneticcauses are nucleotide expansions in C9ORF72 and mutations in SOD1, TARDBP and FUS. We have shown that motor neuron deathis non-cell autonomous and that reducing mutant SOD1 in CNS microglia/peripheral macrophages slows disease progression. This suggests that in ALS, mutant gene expression in microglia/macrophages as well as the natural activation response of these cellsbecome deleterious.

Leader

Leader: 

BOILLEE Séverine
Établissements

École doctorale: 

ED 158 3C
Laboratory

Initiatives d'Excellence: 

IHU-A-ICM, Labex revive
Publications

publications: 

Phenotype difference between ALS patients with expanded repeats in C9ORF72 and patients with mutations in other ALS-related genes. Millecamps S, Boillée S, Le Ber I, Seilhean D, Teyssou E, Giraudeau M, Moigneu C, Vandenberghe N, Danel-Brunaud V, Corcia P, Pradat PF, Le Forestier N, Lacomblez L, Bruneteau G, Camu W, Brice A, Cazeneuve C, Leguern E, Meininger V, Salachas F. J Med Genet. 2012 Apr;49(4):258-63.

Novel UBQLN2 mutations linked to amyotrophic lateral sclerosis and atypical hereditary spastic paraplegia phenotype through defective HSP70-mediated proteolysis. Teyssou E, Chartier L, Amador MD, 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. Neurobiol Aging. 2017 Oct;58:239.e11-239.e20

System xC- is a mediator of microglial function and its deletion slows symptoms in amyotrophic lateral sclerosis mice. Mesci P, Zaïdi S, Lobsiger CS, Millecamps S, Escartin C, Seilhean D, Sato H, Mallat M, Boillée S. Brain. 2015 Jan;138(Pt 1):53-68.

C1q induction and global complement pathway activation do not contribute to ALS toxicity in mutant SOD1 mice. Lobsiger CS, Boillée S, Pozniak C, Khan AM, McAlonis-Downes M, Lewcock JW, Cleveland DW. Proc Natl Acad Sci U S A. 2013 Nov 12;110(46):E4385-92.

The NADPH oxidase Nox2 regulates VEGFR1/CSF-1R-mediated microglial chemotaxis and promotes early postnatal infiltration of phagocytes in the subventricular zone of the mouse cerebral cortex. Lelli A, Gervais A, Colin C, Chéret C, Ruiz de Almodovar C, Carmeliet P, Krause KH, Boillée S, Mallat M. Glia. 2013 Sep;61(9):1542-55.