Reduced microglial activation through the inhibition of colony-stimulating factor 1 receptor (CSF1R) to promote remyelination and neuroprotection

WIES MANCINI V.S.B., PASQUINI J.M., CORREALE J.D., PASQUINI L.A

CABA

Congreso; The role of glial cells in health and disease of the Nervous System: clinical and basic science walking together; 2017

GLIA-Polo Científico y Tecnológico

Multiple Sclerosis (MS) is oneof the most common causes of progressive disability affecting young people, yettherapeutic options available for progressive MS are disappointing and remain achallenge. Demyelination and neurodegeneration involve the activation ofmicroglial cells, which are in turn physiologically dependent oncolony-stimulating factor 1 receptor (CSF-1R) signaling. In the present work,we used microglial modulation through oral administration of brain-penetrantCSF-1R inhibitor BLZ945 and acute and chronic cuprizone (CPZ)-induceddemyelination to evaluate preventive and therapeutic effects onde/remyelination and neurodegeneration. Our results show that BLZ945 induced asignificant reduction in the number of microglia and their shift toward an M2and phagocytic phenotype, without alterations in peripheral macrophages.Preventive BLZ945 treatment attenuated demyelination in both CPZ models, whiletherapeutic treatment promoted remyelination and neuroprotection in the chronicmodel. These results could be potentially transferred to the treatment ofprogressive forms of MS.