Multiple sclerosis (MS) is an autoimmune demyelinating disease in the central nervous system (CNS) characterized by the failure of remyelination (Goverman,2009).Currently,there are no cures for patients with MS (Kotter et al.,2011;Kremer et al.,2011).Remyelination in MS is required to reduce axonal degeneration and subsequent disability.Mature oligodendrocytes (OLs) are the sole myelinating cells of the CNS,new myelinating OLs are generated by differentiation of oligodendrocyte progenitor cells (OPCs) that are abundantly present in the adult CNS (McTigue and Tripathi,2008;Goldman et al.,2012).Inefficiency of OPC differentiation into myelinating OLs is a key factor leading to failure of remyelination.Molecular mech-anisms underlying inhibition of OPC differentiation are not fully understood.Emerging data suggest that the TLRs and their downstream target interleukin-1 receptor-associated kinase 1 (IRAK1) are involved in inhibition of OPC differentiation and remyelination (Sloane et al.,2010;Kremer et al.,2011;Santra et al.,2014).Thus,inactivation of the TLR signaling pathway in OPCs may potentially enhance remyelination by promoting OPCs to differentiation.MicroRNAs (miRNAs),a class of small non-coding RNAs,mediate post transcriptional gene silencing and act as important regulators during development and dis-ease progression (Kosik,2006;Letzen et al.,2010;Li and Yao,2012).MiR-146a has been shown to regulate the TLR pathway (Lu et al.,2010;Ma et al.,2011;Quinn et al.,2013),and is altered in MS patients (Zhao et al.,2011;Guerau-de-Arellano et al.,2012);however,the link of miR-146a to remyelination has not been studied,Therefore,we hypothesized that miR-146a,by inactivation of the TLR signaling pathway,promoting differentiation of OPCs,will enhance remyelination.A toxic demyelin-ation model induced by cuprizone (CPZ) diet was employed.This model induces selectively apoptotic oligodendrocyte death and minimal immune response (Moharregh-Khiabani et al.,2010;Zhang et al.,2016).