Macrophage migration inhibitory factor (MIF) in CNS diseases: Functional regulation and potential therapeutic indication

Macrophage migration inhibitory factor (MIF) is a multifunctional protein that possesses cytokine, enzyme, and endocrine activities and acts as a chaperone-like molecule. Owing to its immune-inflammatory regulatory properties, the role of MIF has long been an attractive target in research on various autoimmune and inflammatory disorders. MIF is also widely expressed in the central nervous system (CNS), and its potential roles in CNS disorders have become a focus to elucidate the physiological and pathological effects of MIF and to explore its potential significance in the treatment of CNS diseases. Previously, the majority of work on MIF functional regulation was focused on MIF tautomerase inhibitors. However, mounting information has indicated that the functions of MIF extend far beyond its tautomerase activity. Here, we review the recent advances in understanding the complex roles of MIF in the pathogenesis of CNS disorders as well as the discovery and design of small molecules targeted to tautomerase and nuclease of MIF.