Cell death in amyotrophic lateral sclerosis: interplay between neuronal and glial cells (Articolo in rivista)

Type
Label
  • Cell death in amyotrophic lateral sclerosis: interplay between neuronal and glial cells (Articolo in rivista) (literal)
Anno
  • 2004-01-01T00:00:00+01:00 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi
  • 10.1096/fj.03-1199fje (literal)
Alternative label
  • Ferri A.; Nencini M.; Casciati A.; Cozzolino M.; Angelini D.F.; Longone P.; Spallone A.; Rotilio G.; Carrì M.T. (2004)
    Cell death in amyotrophic lateral sclerosis: interplay between neuronal and glial cells
    in The FASEB journal
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • Ferri A.; Nencini M.; Casciati A.; Cozzolino M.; Angelini D.F.; Longone P.; Spallone A.; Rotilio G.; Carrì M.T. (literal)
Pagina inizio
  • 1261 (literal)
Pagina fine
  • 1263 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume
  • 18 (literal)
Rivista
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroFascicolo
  • 11 (literal)
Note
  • PubMe (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni
  • IN-Roma (literal)
Titolo
  • Cell death in amyotrophic lateral sclerosis: interplay between neuronal and glial cells (literal)
Abstract
  • Mutations in the gene coding for the ubiquitous, anti-oxidant enzyme Cu,Zn superoxide dismutase (SOD1) are associated with familial amyotrophic lateral sclerosis (fALS), a fatal disease characterized by selective loss of motor neurons. Expression of a mutant SOD1 typical of fALS patients restricted to either motor neurons or astrocytes is insufficient to generate a pathological phenotype in mouse models, suggesting that a deleterious interplay between different cell types is necessary for the pathogenesis of the disease. In this study, we demonstrate the actual role of a functional cross-talk between glial and neuronal cells expressing fALS mutant G93A-SOD1, where an increase in the production of reactive oxygen species occurs. We show that human glioblastoma cells expressing G93A-SOD1 induce activation of caspase-1, release of cytokines, and activation of apoptotic pathways in cocultured human neuroblastoma cells also expressing G93A-SOD1. Activation of caspase-1 and caspase-3 is observed also in neuroblastoma lines expressing other fALS-SOD1s (G37R, G85R, and I113T) cocultured with glioblastoma lines expressing the corresponding mutant enzymes. These effects are consequent to activation of inflammatory processes in G93A-glioblastoma cells stimulated by cocultured G93A-neuroblastoma. Furthermore, selective death of embryonal spinal motor neurons from G93A-SOD1 transgenic mice is induced by coculture with G93A-glioblastoma and prevented by inhibition of NO synthase. Proinflammatory cytokines, interferon-gamma, and nitric oxide are among the molecular signals exchanged between glial and neuronal cells that generate a functional interplay between the two cell types. This cross-talk may be crucial for the pathogenesis of SOD1-linked fALS but also for the more common sporadic form of the disease, where markers of increased oxidative stress and of glial activation have been found. (literal)
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