MIF, a 12.5 kDa cytokine discovered in 1993, is produced by T cells and modulates the inflammatory responses [1]. It plays an important role in autoimmune diseases by interacting with various receptors and proteins, disturbing cellular signaling pathways and immune responses [1], [2]. MIF, binding to membrane receptors like CD74, CXCR2, CXCR4, and CXCR7, initiates a variety of signaling pathways [3]. The interaction of MIF with the CD74 receptor is essential for its activation [3], [4]. Predominantly located in the cytoplasm, MIF is induced by proinflammatory factors like LPS, tumor necrosis factor (TNF)-α, as well as hypoxia, hydrogen peroxide (H2O2), and thrombosis [5], [6], [7], [8], [9]. Furthermore, the expression of MIF is tightly regulated by many transcription factors, including SP1, NF-κB, HBP1, CREB, and HIF-1 [10], [11], [12], [13].

Notably, MIF has been implicated in modulating the function of various components of the nervous system, such as neurons, glia, and endothelial cells (ECs) [14]. It induced neuroinflammation with its chemokine-like activity and contributes to cell death with a nucleic acid enzymatic activity. Recent research has highlighted the potential association between MIF and cognitive impairment diseases. However, there is a lack of systematical discussion regarding the effects and molecular mechanism of MIF in cognitive impairment disorders. Hence, the primary aim of this review is to provide a thorough analysis of the relationship between them. Moreover, we present a concise overview of the experimental utilization of MIF inhibitors in the management of cognitive impairment disorders, emphasizing their potential for future clinical use. Fig. 1, Fig. 2, Fig. 3