title: Mechanisms of tissue injury in multiple sclerosis: opportunities for neuroprotective therapy.
abstract: Development of neuroprotective therapies for multiple sclerosis is dependent on defining the precise mechanisms whereby immune effector cells and molecules are able to induce relatively selective injury of oligodendrocytes (OLs) and their myelin membranes. The selectivity of this injury could be conferred either by the properties of the effectors or the targets. The former would involve antigen specific recognition by either antibody or T cell receptor of the adaptive immune system. OLs are also susceptible to non antigen restricted injury mediated by components of the innate immune system including 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 intracellular signaling pathways, including the caspase cascade. Development of therapeutic delivery systems, which would reach the site of disease activity within the CNS, will permit the administration of inhibitors either of the cell death pathway or of effector target interaction and opens new avenues to neuroprotection approach.
authors: Neuroimmunology Unit, Montreal Neurological Institute, McGill University, Quebec, Canada. mbar@musica.mcgill.ca
authors: S
authors: S
authors: Pouly
authors: J P
authors: JP
authors: Antel
authors: U
authors: U
authors: Ladiwala
authors: J
authors: J
authors: Nalbantoglu
authors: B
authors: B
authors: Becher
mesh_terms: D001327:Autoimmune Diseases / Q000473:pathology; D002493:Central Nervous System Diseases / Q000473:pathology; D006801:Humans; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000209:etiology / Q000276:immunology / Q000503:physiopathology*; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D009836:Oligodendroglia / Q000473:pathology / Q000502:physiology; D050378:T-Lymphocytes, Regulatory / Q000502:physiology
chemical_list: D018696:Neuroprotective Agents