Potential Roles of Myeloid Differentiation Factor 2 on Neuroinflammation and Its Possible Interventions

Neuroinflammation is the primary response by immune cells in the nervous system to protect against infection. Chronic and uncontrolled neuroinflammation triggers neuronal injury and neuronal death resulting in a variety of neurodegenerative disorders. Therefore, fine tuning of the immune response in the nervous system is now extensively considered as a potential therapeutic intervention for those diseases. The immune cells of the nervous system express Toll-like receptor 4 (TLR4) together with myeloid differentiation factor 2 (MD-2) to protect against the pathogens. Over the last 10 years, antagonists targeting the functional domains of MD-2 have become attractive pharmacological intervention strategies in pre-clinical studies into neuroinflammation and its associated brain pathologies. This review aims to summarize and discuss the roles of TLR4-MD-2 signaling pathway activation in various models of neuroinflammation. This review article also highlights the studies reporting the effect of MD-2 antagonists on neuroinflammation in in vitro and in vivo studies.