Brain : a journal of neurology
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Demyelinating disorders of the central nervous system are among the most crippling neurological diseases affecting patients at various stages of life. In the most prominent demyelinating disease, multiple sclerosis, the regeneration of myelin sheaths often fails due to a default of the resident stem/precursor cells (oligodendrocyte precursor cells) to differentiate into mature myelin forming cells. Significant advances have been made in our understanding of the molecular and cellular processes involved in remyelination. ⋯ The pattern by which remyelination inducers and inhibitors are expressed in multiple sclerosis lesions may determine a window of opportunity during which oligodendrocyte precursor cells can successfully differentiate. As the first molecules aiming at promoting remyelination are about to enter clinical trials, this review critically evaluates recent advances in our understanding of the biology of oligodendrocyte precursor cells and of the stage-dependent molecular pathology of multiple sclerosis lesions relevant to the regeneration of myelin sheaths. We propose a model that may help to provide cues for how remyelination can be therapeutically enhanced in clinical disease.