Immune-mediated oligodendrocyte injury in multiple sclerosis: Molecular mechanisms and therapeutic interventions

Abstract

In this review, new insights into the immunopathogenesis of multiple sclerosis (MS) are discussed, with special focus on the potential mechanisms leading to neuroinflammation in MS-that is, the role of autoreactive T cells, infections, and neurodegenerative events. Oligodendrocytes are considered to be the target of autoimmune inflammation in the CNS of MS patients. Some important features of oligodendrocyte biology are discussed, together with the molecular mechanisms that are potentially involved in oligodendrocyte injury. These include injury mechanisms that might be executed by the adaptive and innate immune system, via cytokines and/or oligodendrocyte receptors, or as a consequence of nitrative and oxidative stress, and excitotoxicity. The mode of cell death of oligodendrocytes in MS is discussed, in addition to the mechanisms of axonal injury as observed in pathology- and imaging-based studies. Finally, recent progress in therapeutic strategies that may interfere with these pathological processes are reviewed, with a focus on repair strategies, such as gene therapy, antibody-mediated remyelination, and stem cell therapy.