Molekulare Analyse CD95-mediierter Signalwege im Nervensystem

• Applicant: Professorin Dr. Ana Martin-Villalba
• Subject Area: Molecular and Cellular Neurology and Neuropathology
• Term: from 2006 to 2008
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 20865879

The CD95 (Apo-1/Fas)/CD95 ligand (CD95L) system is best characterized as a trigger of apoptosis. Nevertheless, despite broad expression of CD95L and CD95 in the developing brain, at these stages triggering of CD95 does not induce apoptosis. To our surprise, triggering of CD95 in neural stem cells (NSCs) or cultured immature neurons induces neurogenesis or substantially increases neurite branches, respectively. In another undifferentiated system, glioma cells resistant to CD95- induced apoptosis, triggering of CD95 increased invasion. Our data indicate that inhibition of glycogen synthase kinase (GSK) is a common denominator of these nonapoptotic pathways downstream of CD95. In this study we plan to work out the molecules signaling neurogenesis, branching or invasion through GSK. In addition, we want to find out the molecules signaling inhibition of GSK downstream of CD95. Insight into this signaling pathway should ultimately result in the development of therapies able to (1) harness endogenous NSCs for the repair of the diseased brain; (2) induce regeneration (branching/sprouting) in the adult injured brain; (3) block invasion of glioblastoma tumors resistant to CD95-induced apoptosis.

• DFG Programme: Research Grants