title: Fas/CD95 regulatory protein Faim2 is neuroprotective after transient brain ischemia.
abstract: Death receptor (DR) signaling has a major impact on the outcome of numerous neurological diseases, including ischemic stroke. DRs mediate not only cell death signals, but also proinflammatory responses and cell proliferation. Identification of regulatory proteins that control the switch between apoptotic and alternative DR signaling opens new therapeutic opportunities. Fas apoptotic inhibitory molecule 2 (Faim2) is an evolutionary conserved, neuron-specific inhibitor of Fas/CD95-mediated apoptosis. To investigate its role during development and in disease models, we generated Faim2-deficient mice. The ubiquitous null mutation displayed a viable and fertile phenotype without overt deficiencies. However, lack of Faim2 caused an increase in susceptibility to combined oxygen-glucose deprivation in primary neurons in vitro as well as in caspase-associated cell death, stroke volume, and neurological impairment after cerebral ischemia in vivo. These processes were rescued by lentiviral Faim2 gene transfer. In summary, we provide evidence that Faim2 is a novel neuroprotective molecule in the context of cerebral ischemia.
authors.affiliation: Department of Neurology, University Hospital and Medical School, RWTH Aachen University, D-52074 Aachen, Germany.
authors.forename: Arno
authors.initials: A
authors.lastname: Reich
authors.forename: Christopher
authors.initials: C
authors.lastname: Spering
authors.forename: Karen
authors.initials: K
authors.lastname: Gertz
authors.forename: Christoph
authors.initials: C
authors.lastname: Harms
authors.forename: Ellen
authors.initials: E
authors.lastname: Gerhardt
authors.forename: Golo
authors.initials: G
authors.lastname: Kronenberg
authors.forename: Klaus A
authors.initials: KA
authors.lastname: Nave
authors.forename: Markus
authors.initials: M
authors.lastname: Schwab
authors.forename: Simone C
authors.initials: SC
authors.lastname: Tauber
authors.forename: Anja
authors.initials: A
authors.lastname: Drinkut
authors.forename: Kristian
authors.initials: K
authors.lastname: Harms
authors.forename: Chrstioph P
authors.initials: CP
authors.lastname: Beier
authors.forename: Aaron
authors.initials: A
authors.lastname: Voigt
authors.forename: Sandra
authors.initials: S
authors.lastname: Göbbels
authors.forename: Matthias
authors.initials: M
authors.lastname: Endres
authors.forename: Jörg B
authors.initials: JB
authors.lastname: Schulz
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D020520:Brain Infarction / Q000209:etiology / Q000517:prevention & control*; D053148:Caspase 3 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D016923:Cell Death / Q000235:genetics; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000235:genetics; D005947:Glucose / Q000172:deficiency; D049452:Green Fluorescent Proteins / Q000235:genetics; D000860:Hypoxia; D020287:In Situ Nick-End Labeling / Q000379:methods; D002546:Ischemic Attack, Transient / Q000150:complications* / Q000235:genetics / Q000473:pathology*; D008565:Membrane Proteins / Q000172:deficiency / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000378:metabolism*; D009422:Nervous System Diseases / Q000209:etiology / Q000517:prevention & control; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D013997:Time Factors; D014162:Transfection / Q000379:methods; D019014:fas Receptor / Q000235:genetics / Q000378:metabolism*
chemical_list: D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D019014:fas Receptor; C523971:lifeguard protein, mouse; D049452:Green Fluorescent Proteins; D053148:Caspase 3; D053181:Caspase 8; D010751:Phosphopyruvate Hydratase; D005947:Glucose