title: M1 and M2 Functional Imprinting of Primary Microglia: Role of P2X7 Activation and miR-125b.
abstract: Amyotrophic lateral sclerosis (ALS) is a most frequently occurring and severe form of motor neuron disease, causing death within 3-5 years from diagnosis and with a worldwide incidence of about 2 per 100,000 person-years. Mutations in over twenty genes associated with familial forms of ALS have provided insights into the mechanisms leading to motor neuron death. Moreover, mutations in two RNA binding proteins, TAR DNA binding protein 43 and fused in sarcoma, have raised the intriguing possibility that perturbations of RNA metabolism, including that of the small endogenous RNA molecules that repress target genes at the posttranscriptional level, that is, microRNAs, may contribute to disease pathogenesis. At present, the mechanisms by which microglia actively participate to both toxic and neuroprotective actions in ALS constitute an important matter of research. Among the pathways involved in ALS-altered microglia responses, in previous works we have uncovered the hyperactivation of P2X7 receptor by extracellular ATP and the overexpression of miR-125b, both leading to uncontrolled toxic M1 reactions. In order to shed further light on the complexity of these processes, in this short review we will describe the M1/M2 functional imprinting of primary microglia and a role played by P2X7 and miR-125b in ALS microglia activation.
authors.affiliation: CNR-Institute of Cell Biology and Neurobiology, Via del Fosso di Fiorano 65, 00143 Rome, Italy; Fondazione Santa Lucia, Via del Fosso di Fiorano 65, 00143 Rome, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Parisi
authors.affiliation: Fondazione Santa Lucia, Via del Fosso di Fiorano 65, 00143 Rome, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Napoli
authors.affiliation: Inflammation and Experimental Surgery Unit, CIBERehd, Biomedical Research Institute of Murcia (IMIB-Arrixaca), Clinical University Hospital Virgen de la Arrixaca, 30120 Murcia, Spain.
authors.forename: Pablo
authors.identifier: 0000-0002-9688-1804
authors.initials: P
authors.lastname: Pelegrin
authors.affiliation: CNR-Institute of Cell Biology and Neurobiology, Via del Fosso di Fiorano 65, 00143 Rome, Italy; Fondazione Santa Lucia, Via del Fosso di Fiorano 65, 00143 Rome, Italy.
authors.forename: Cinzia
authors.identifier: 0000-0001-7362-8307
authors.initials: C
authors.lastname: Volonté
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000378:metabolism*; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D006801:Humans; D007249:Inflammation; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D017628:Microglia / Q000378:metabolism*; D009046:Motor Neurons / Q000378:metabolism; D009154:Mutation; D010641:Phenotype; D058486:Receptors, Purinergic P2X7 / Q000378:metabolism*; D015398:Signal Transduction; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D019208:Brain-Derived Neurotrophic Factor; C531888:MIRN125 microRNA, human; D035683:MicroRNAs; C527468:Mirn125 microRNA, mouse; C546468:P2RX7 protein, human; D058486:Receptors, Purinergic P2X7; C579455:BDNF protein, human; D013482:Superoxide Dismutase