Fibroblast growth factor 9 inhibits remyelination via an off target effect on astrocytes in multiple sclerosis

Failure of remyelination in multiple sclerosis (MS) is associated with inhibition of oligodendrocyte precursor (OPC) differentiation, but the cellular and molecular mechanisms involved remain poorly understood. We now report inflammatory demyelination in MS is associated with localized expression of fibroblast growth factor 9 (FGF9) by oligodendrocytes and to a lesser extent astrocytes, and demonstrate FGF9 inhibits myelination and remyelination in vitro. This inhibitory activity is reversible and due to an off target FGF9-dependent effect on astrocytes that disrupts in the growth factor milieu required to support myelination.

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Lindner M, Thümmler K, Arthur A, Brunner S, Elliott C, McElroy D, Mohan H, Williams A, Edgar JM, Schuh C, Stadelmann C, Barnett SC, Lassmann H, Mücklisch S, Mudaliar M, Schaeren-Wiemers N, Meinl E, Linington C