The two sides of Faim2 -- modulation of cell death and regeneration

Abstract

Most neurologic diseases are associated with neuronal cell death, and the surviving neurons consequently initiate regenerative processes. Activation of Fas/CD95, a so-called death receptor, can induce both apoptosis and alternative, non-apoptotic intracellular signaling 1 . Consequently, modulators of the Fas/CD95 signaling pathways have gained importance. We have investigated the role of one such mudulator, Fas inhibitory molecule 2 (Faim2), in neurologic diseases. We generated a Faim2 deficient mouse line and applyed models of transient cerebral ischemia, bacterial meningitis, and Parkinson disease 2-4 . In brief, we found increased neuronal cell death in the acute phase of all disease models in Faim2 deficient mice in comparison to the Faim2 wildtype (WT). In addition, signs of increased regeneration in Faim2 deficient mice point towards an involvement of Faim2 and Fas/CD95 in regenerative processes. Finally, we found disease stage-dependent regulation of Faim2 expression, potentially enabling the switch between apoptotic and alternative Fas/CD95 signaling. Thus, Faim2 appears to be an interesting protein for two reasons. First, it could be a target protein for neuroprotective strategies in the above mentioned diseases. Second, it may help us to understand the cellular signaling pathways involved in neuronal cell death and in regeneration. In spite of its name, Faim2 is not well known. We therefore start with nomenclature issues before describing the neurobiology of Faim2 in more detail. What do we know about Faim2?