Amyotrophic Lateral Sclerosis (ALS)

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

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: 

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.

 

Fonctions et différenciation des cellules microgliales

Domaine de recherche principal: 

Neuropharmacology / cell signaling

Mots clefs: 

Neuroinflammation
Microglia
CNS development
Amyotrophic Lateral Sclerosis (ALS)
Alzheimer’s Disease (AD)

Labelisation ENP: 

2007

Code unité de recherche: 

UMRS975 UMR7225

Notre recherche se concentre sur le rôle de la microglie et les mécanismes qui déterminent le recrutement des cellules microgliales au cours du développement normal ou de maladies neurodégénératives. Nous avons montré que la microglie exprime deux types de NADPH oxydases, NoX1 et Nox2, qui régulent leur capacité à produire des cytokines et espèces réactives de l'oxygènes neurotoxiques, responsables de lésions neuronales dans des contextes neuro-inflammatoires.

Établissements

Établissement de rattachement: 

Université Pierre et Marie Curie

Établissements affiliés: 

Inserm
CNRS

Université: 

Université Pierre et Marie Curie

École doctorale: 

ED158
Publications

publications: 

Effect of Exposure to 1,800 MHz Electromagnetic Fields on Heat Shock Proteins and Glial Cells in the Brain of Developing Rats. Watilliaux A, Edeline JM, Lévêque P, Jay TM, Mallat M. Neurotox Res. 2011 Aug;20(2):109-19

Schwann cells expressing dismutase active mutant SOD1 unexpectedly slow disease progression in ALS mice. Lobsiger CS, Boillee S, McAlonis-Downes M, Khan AM, Feltri ML, Yamanaka K, Cleveland DW. Proc Natl Acad Sci USA. 106:4465-70. (2009)

Mutant SOD1 in cell types other than motor neurons and oligodendrocytes accelerates onset of disease in ALS mice. Yamanaka K*, Boillée S*, Roberts EA*, Garcia ML, McAlonis-Downes M, Miske O, Cleveland DW, Goldstein LS. Proc Natl Acad Sci USA. 105:7594-9. (* equal contribution). (2008)

Neurotoxic activation of microglia is promoted by a Nox1-dependent NADPH oxidaseCheret C, Gervais A,  Colin C, Lelli A, Amar L, Ravassard P, Mallet J, Cumano A, Krause KH, Mallat M.J. Neurosci  28: 12039-51 (2008)