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Fas/CD95 Regulatory Protein Faim2 Is Neuroprotective after Transient Brain Ischemia

2011; Society for Neuroscience; Volume: 31; Issue: 1 Linguagem: Inglês

10.1523/jneurosci.2188-10.2011

1529-2401

Arno Reich, Christopher Spering, Karen Gertz, Christoph Harms, Ellen Gerhardt, Golo Kronenberg, Klaus Armin Nave, Markus H. Schwab, Simone C. Tauber, Anja Drinkut, Kristian Harms, Christoph P. Beier, Aaron Voigt, Sandra Göbbels, Matthias Endres, Jörg B. Schulz,

Phagocytosis and Immune Regulation

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.