Abstract
Background : There is growing evidence that microglia are key players in the pathological process of amyotrophiclateral sclerosis (ALS). It is suggested that microglia have a dual role in motoneurone degeneration through therelease of both neuroprotective and neurotoxic factors.Results : To identify candidate genes that may be involved in ALS pathology we have analysed at early symptomaticage (P90), the molecular signature of microglia from the lumbar region of the spinal cord of hSOD1G93Amice, the mostwidely used animal model of ALS. We first identified unique hSOD1G93Amicroglia transcriptomic profile that, in additionto more classical processes such as chemotaxis and immune response, pointed toward the potential involvement of thetumour suppressor gene breast cancer susceptibility gene 1(Brca1). Secondly, comparison with our previous data onhSOD1G93Amotoneurone gene profile substantiated the putative contribution of Brca1 in ALS. Finally, we establishedthat 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 andthe involvement of microglia in ALS. Importantly, the identification of Brca1 as a novel microglial marker and as possiblecontributor in both human and animal model of ALS may represent a valid therapeutic target. Moreover, our data pointstoward novel research strategies such as investigating the role of oncogenic proteins in neurodegenerative diseases.