Investigating the mechanism of TNFalpha mediated cell death in oligodendrocytes

The goal of this proposal is to explore the role and mechanism of necroptosis inmediating oligodendrocyte cell death induced by TNF and the contribution of this pathway toprogressive demyelination, inflammation and neurodegeneration in animal models of multiple sclerosis(MS). MS, an inflammatory demyelinating disease of the central nervous system (CNS), is the mostcommon chronic neurodegenerative disease for young adults during their most productive ages. Wepropose to use necrostatins and genetic models and cellular and biochemical approaches to investigatethe role and mechanism of RIP1 kinases in mediating the death of oligodendrocytes in TNFR1 pathwayand the involvement of necroptosis in demyelination, inflammation and neurodegeneration in animalmodels of MS