title: Brca1 is expressed in human microglia and is dysregulated in human and animal model of ALS.
abstract: 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.
authors.affiliation: Institute for Neurosciences of Montpellier (INM), INSERM U1051, 80, rue Augustin Fliche, 34091, Montpellier, Cedex 5, France. harun.noristani@ibn-lab.com.
authors.forename: Harun Najib
authors.initials: HN
authors.lastname: Noristani
authors.affiliation: "Integrative Biology of Neurodegeneration", IKERBASQUE Basque Foundation for Science and Neuroscience Department, University of the Basque Country, Bilbao, Spain. jcsabourin@hotmail.fr.
authors.forename: Jean Charles
authors.initials: JC
authors.lastname: Sabourin
authors.affiliation: Institute for Neurosciences of Montpellier (INM), INSERM U1051, 80, rue Augustin Fliche, 34091, Montpellier, Cedex 5, France. yannick.gerber@ibn-lab.com.|"Integrative Biology of Neurodegeneration", IKERBASQUE Basque Foundation for Science and Neuroscience Department, University of the Basque Country, Bilbao, Spain. yannick.gerber@ibn-lab.com.
authors.forename: Yannick Nicolas
authors.initials: YN
authors.lastname: Gerber
authors.affiliation: Institute for Neurosciences of Montpellier (INM), INSERM U1051, 80, rue Augustin Fliche, 34091, Montpellier, Cedex 5, France. mteigell@univ-montp2.fr.
authors.forename: Marisa
authors.initials: M
authors.lastname: Teigell
authors.affiliation: Kantonspital St. Gallen. FachMuskelzentrum/ALS clinic, St. Gallen, Switzerland. andreas.sommacal@kssg.ch.
authors.forename: Andreas
authors.initials: A
authors.lastname: Sommacal
authors.affiliation: CIC bioGUNE, Cell Biology & Stem Cells Unit, Technological Park of Bizkaia, Derio, Spain. mdmvivanco@cicbiogune.es.
authors.forename: Maria dM
authors.initials: Md
authors.lastname: Vivanco
authors.affiliation: Kantonspital St. Gallen. FachMuskelzentrum/ALS clinic, St. Gallen, Switzerland. markus.weber@kssg.ch.
authors.forename: Markus
authors.initials: M
authors.lastname: Weber
authors.affiliation: Institute for Neurosciences of Montpellier (INM), INSERM U1051, 80, rue Augustin Fliche, 34091, Montpellier, Cedex 5, France. florence.perrin@inserm.fr.|"Integrative Biology of Neurodegeneration", IKERBASQUE Basque Foundation for Science and Neuroscience Department, University of the Basque Country, Bilbao, Spain. florence.perrin@inserm.fr.|Department "Biologie-Mécanismes du Vivant" Faculty of Science, University of Montpellier, Montpellier, France. florence.perrin@inserm.fr.
authors.forename: Florence Evelyne
authors.initials: FE
authors.lastname: Perrin
mesh_terms: D000367:Age Factors; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D019313:BRCA1 Protein / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D004249:DNA Damage; D004195:Disease Models, Animal; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks; D005911:Gliosis / Q000235:genetics / Q000473:pathology; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D017628:Microglia / Q000378:metabolism*; D009046:Motor Neurons / Q000378:metabolism; D020125:Mutation, Missense; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D017354:Point Mutation; D011994:Recombinant Proteins; D013116:Spinal Cord / Q000166:cytology; D013482:Superoxide Dismutase / Q000096:biosynthesis / Q000235:genetics; D000072105:Superoxide Dismutase-1; D059467:Transcriptome; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D015854:Up-Regulation
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human; C000605931:Brca1 protein, mouse; D009419:Nerve Tissue Proteins; D011994:Recombinant Proteins; C000606290:SOD1 protein, human; D025521:Tumor Suppressor Proteins; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1