Mechanisms of tissue injury in multiple sclerosis: opportunities for neuroprotective therapy

Development of neuroprotective therapies for multiple sclerosis is dependen t on defining the precise mechanisms whereby immune effector cells and mole cules are able to induce relatively selective injury of oligodendrocytes (O Ls) and their myelin membranes. The selectivity of this injury could be con ferred either by the properties of the effecters or the targets. The former would involve antigen specific recognition by either antibody or T cell re ceptor of the adaptive immune system. OLs are also susceptible to non antig en restricted injury mediated by components of the innate immune system inc luding macrophages/microglia and NK cells. Target related selectivity could reflect the expression of death inducing surface receptors (such as Fas or TNFR-1) required for interaction with effector mediators and subsequent in tracellular signaling pathways, including the caspase cascade. Development of therapeutic delivery systems, which would reach the site of disease acti vity within the CNS, will permit the administration of inhibitors either of the cell death pathway or of effector target interaction and opens new ave nues to neuroprotection approach.