Brca1 is expressed in human microglia and is dysregulated in human and animal model of ALS

Autor: Noristani, Harun Najib, Sabourin, Jean Charles, Gerber, Yannick Nicolas, Teigell, Marisa, Sommacal, Andreas, dM Vivanco, Maria, Weber, Markus, Perrin, Florence Evelyne
Přispěvatelé: Institut des Neurosciences de Montpellier - Déficits sensoriels et moteurs (INM), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Science and Neuroscience Department [Bilbao, Spain], Integrative Biology of Neurodegeneration [Bilbao, Spain], Fundación Ikerbasque [Bilbao]-University of the Basque Country-Fundación Ikerbasque [Bilbao]-University of the Basque Country, Deutsches Forschungszentrum für Künstliche Intelligenz GmbH = German Research Center for Artificial Intelligence (DFKI), Mécanismes moléculaires dans les démences neurodégénératives (MMDN), Université de Montpellier (UM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL), Institut des Neurosciences de Montpellier (INM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Ikerbasque - Basque Foundation for Science-University of the Basque Country-Ikerbasque - Basque Foundation for Science-University of the Basque Country, École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Perrin, Florence
Jazyk: angličtina
Rok vydání: 2015
Předmět:
Zdroj: Molecular Neurodegeneration
Molecular Neurodegeneration, BioMed Central, 2015, 10 (1), ⟨10.1186/s13024-015-0023-x⟩
Addi. Archivo Digital para la Docencia y la Investigación
instname
ISSN: 1750-1326
DOI: 10.1186/s13024-015-0023-x⟩
Popis: Background: There is growing evidence that microglia are key players in the pathological process of amyotrophic lateral sclerosis (ALS). It is suggested that microglia have a dual role in motoneurone degeneration through the release of both neuroprotective and neurotoxic factors. Results: To identify candidate genes that may be involved in ALS pathology we have analysed at early symptomatic age (P90), the molecular signature of microglia from the lumbar region of the spinal cord of hSOD1(G93A) mice, the most widely used animal model of ALS. We first identified unique hSOD1(G93A) microglia transcriptomic profile that, in addition to more classical processes such as chemotaxis and immune response, pointed toward the potential involvement of the tumour suppressor gene breast cancer susceptibility gene 1 (Brca1). Secondly, comparison with our previous data on hSOD1(G93A) motoneurone gene profile substantiated the putative contribution of Brca1 in ALS. Finally, we established that Brca1 protein is specifically expressed in human spinal microglia and is up-regulated in ALS patients. Conclusions: Overall, our data provide new insights into the pathogenic concept of a non-cell-autonomous disease and the involvement of microglia in ALS. Importantly, the identification of Brca1 as a novel microglial marker and as possible contributor in both human and animal model of ALS may represent a valid therapeutic target. Moreover, our data points toward novel research strategies such as investigating the role of oncogenic proteins in neurodegenerative diseases. We are grateful to ALS patients and their relatives that donate their tissues. We acknowledge the New York Brain Bank-The Taub Institute, Columbia University (NYBB). The hybridoma CD11b antibody developed by Timothy A. Springer was obtained from the Developmental Studies Hybridoma Bank developed under the auspices of the NICHD and maintained by the University of Iowa, Department of Biology, Iowa city, IA 52242. We thank the iGE3Genomics Platform, University of Geneva Switzerland for their assistance in transcriptomic and qPCR analysis. This work was supported by the Spanish Government, Plan Nacional de I+D+I 2008-2011 and ISCIII-Subdireccion General de Evaluacion y Fomento de la investigacion (PI10/00709) [to FEP], the Government of the Basque Country grant (Proyectos de Investigacion Sanitaria and Fondo Comun de Cooperacion Aquitania-Euskadi) [to FEP], the "Fondation pour la Recherche Medicale" [to FEP] and the French Government, ANR-FNS grant, GliALS (No ANR-14-CE36-0009-01) [to FEP], the patient organisations "Demain Debout Aquitaine" [to YNG and HNN] and "Verticale" [to FEP and HNN].
Databáze: OpenAIRE
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