The roles played by TLR4 in the pathogenesis of multiple sclerosis; A systematic review article

•Multiple sclerosis (MS) is a pro-inflammatory based disease with un-known main mechanisms.•Toll like receptor 4 (TLR4) uses two well-known intracellular signaling pathways.•TLR4 helps remyelination by increased phagocytosis of myelin debris and inflammation inhibition.•TLR4 also induces demyelination and inflammation, which deteriorate MS pathogenesis.•Increased TLR4 ligands/CD14 and altered the related cells significantly alter the TLR4 functions. Multiple sclerosis (MS) is a world-wide pro-inflammatory based disease, which is prevalent among young individuals. The etiology of the disease and its related complications are yet to be clarified. It has been hypothesized that environmental factors, including pathogen-associated molecular patterns (PAMPs) and the internal factors such as damage-associated molecular patterns (DAMPs), may be the most important inducers/stimulators of the disorder and its related complications. Previous investigations proved that pathogen recognition receptors (PRRs) are the main sensors for the PAMPs and DAMPs. Therefore, it seems that the PRRs have been considered to be the plausible molecules participating in the etiology of MS. Toll-like receptors (TLRs) have been the widely studied PRRs and their roles have been documented in human-related diseases. TLR4 is the main PRR expressed on the cell surface of several immune cells including macrophages and dendritic cells. Several investigations reported that TLR4 to be the main molecule involved in the pathogenesis of pro-inflammatory based diseases. Thus, it has been hypothesized that TLR4 may be a part of the MS puzzle. This review article discusses the role of TLR4 in the MS pathogenesis using recent in vitro and in vivo investigations.