[en] Neuroinflammation is a hallmark of Amyotrophic Lateral Sclerosis (ALS) in hSOD1G93A mouse models where microglial cells contribute to the progressive motor neuron degenerative process. S100-A8 and S100-A9 (also known as MRP8 and MRP14, respectively) are cytoplasmic proteins expressed by inflammatory myeloid cells, including microglia and macrophages. Mainly acting as a heterodimer, S100-A8/A9, when secreted, can activate Toll-like Receptor 4 on immune cells, leading to deleterious proinflammatory cytokine production. Deletion of S100a9 in Alzheimer's disease mouse models showed a positive outcome, reducing pathology. We now assessed its role in ALS. Unexpectedly, our results show that deleting S100a9 in hSOD1G93A ALS mice had no impact on mouse survival, but rather accelerated symptoms with no impact on microglial activation and motor neuron survival, suggesting that blocking S100-A9 would not be a valuable strategy for ALS.
Disciplines :
Neurology
Author, co-author :
Ribon, Matthieu; Sorbonne Université, Institut du Cerveau - Paris Brain Institute - ICM, Inserm, CNRS, Paris, France
Leone, Céline; Sorbonne Université, Institut du Cerveau - Paris Brain Institute - ICM, Inserm, CNRS, Paris, France
Chiot, Aude; Sorbonne Université, Institut du Cerveau - Paris Brain Institute - ICM, Inserm, CNRS, Paris, France
Berriat, Félix; Sorbonne Université, Institut du Cerveau - Paris Brain Institute - ICM, Inserm, CNRS, Paris, France
Rampanana, Martine ; Sorbonne Université, Institut du Cerveau - Paris Brain Institute - ICM, Inserm, CNRS, Paris, France
Cottin, Julie; Sorbonne Université, Institut du Cerveau - Paris Brain Institute - ICM, Inserm, CNRS, Paris, France
Bohl, Delphine; Sorbonne Université, Institut du Cerveau - Paris Brain Institute - ICM, Inserm, CNRS, Paris, France
Millecamps, Stéphanie ; Sorbonne Université, Institut du Cerveau - Paris Brain Institute - ICM, Inserm, CNRS, Paris, France
Lobsiger, Christian S; Sorbonne Université, Institut du Cerveau - Paris Brain Institute - ICM, Inserm, CNRS, Paris, France
HENEKA, Michael ; Department of Neurodegenerative Disease and Gerontopsychiatry/Neurology, University of Bonn Medical Center, German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany
Boillée, Séverine; Sorbonne Université, Institut du Cerveau - Paris Brain Institute - ICM, Inserm, CNRS, Paris, France. Electronic address: severine.boillee@sorbonne-universite.fr
External co-authors :
yes
Language :
English
Title :
Deletion of the inflammatory S100-A9/MRP14 protein does not influence survival in hSOD1G93A ALS mice.
We kindly thank Pr. Thomas Vogl (Institute of Immunolgy Münster, Germany), Drs. Olivier Dussurget and Marie-Anne Nahori (Pasteur Institute, Paris, France) for providing S100a9-/- mice. We thank the technical staff from our animal housing facility (UMS28, Centre d'expérimentation fonctionnelle, Paris, France) and the following ICM core facilities (Paris, France): iGenSeq, Histomics, ICM.Quant (which received ANR-10-IAIHU-06 funding). This study was funded by: ERA-NET NEURON (ANR-14-NEUR-0003-02), ARSLA, Fondation Thierry Latran, NRJ-Institut de France, l'ARMC, S.L.A.F.R., 'La longue route des malades de la SLA', 'Un pied devant l'autre' and private donors to ALS at the ICM.We kindly thank Pr. Thomas Vogl (Institute of Immunolgy M?nster, Germany), Drs. Olivier Dussurget and Marie-Anne Nahori (Pasteur Institute, Paris, France) for providing S100a9-/- mice. We thank the technical staff from our animal housing facility (UMS28, Centre d'exp?rimentation fonctionnelle, Paris, France) and the following ICM core facilities (Paris, France): iGenSeq, Histomics, ICM.Quant (which received ANR-10-IAIHU-06 funding). This study was funded by: ERA-NET NEURON (ANR-14-NEUR-0003-02), ARSLA, Fondation Thierry Latran, NRJ-Institut de France, l'ARMC, S.L.A.F.R. 'La longue route des malades de la SLA', 'Un pied devant l'autre' and private donors to ALS at the ICM.
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