Inhibiting Pde4 could be a way to enhance remyelination in chronic demyelinating diseases
Inhibition of phosphodiesterase-4 promotes oligodendrocyte precursor cell differentiation and enhances CNS remyelination
MS is a devastating disease that involves the loss of myelin, the protective sheaths around axons that enhance impulse con- duction. The increasing effectiveness of new drugs that slow the progression of MS has opened up opportunities for medicines that enhance remyelination and potentially slow disease progression even further. Although several new targets for therapeutic enhancement of remyelination have emerged, few lend themselves readily to conventional drug development.
This study identifies cAMP-Erk1/2/p38Mapk-Creb1 signalling as a functionally important intracellular signalling cascade for CNS remyelination that is regulated at the earliest stages of OPC differentiation. Our results suggest that inhibiting Pde4 could be a way to enhance remyelination in chronic demyelinating diseases, such as MS. Pde4 inhibitors are already approved and used to treat other diseases, so there is great potential for rapid translation of this discovery into clinical practice.
Journal: EMBO Molecular Medicine