Zhang Yu, Yu Zhexiang, Ye Na, Zhen Xuechu
Jiangsu Key Laboratory of Neuropsychiatric Diseases and College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, China.
Department of Pharmacy, Hubei Provincial Clinical Research Center for Parkinson's Disease, Xiangyang Key Laboratory of Movement Disorders, Xiangyang No.1 People' Hospital, Hubei University of Medicine, Xiangyang 441000, China.
Fundam Res. 2023 May 30;4(6):1375-1388. doi: 10.1016/j.fmre.2023.05.008. eCollection 2024 Nov.
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.
巨噬细胞迁移抑制因子（MIF）是一种多功能蛋白，具有细胞因子、酶和内分泌活性，并作为一种分子伴侣样分子发挥作用。由于其免疫炎症调节特性，长期以来，MIF的作用一直是各种自身免疫性和炎症性疾病研究中一个有吸引力的靶点。MIF在中枢神经系统（CNS）中也广泛表达，其在中枢神经系统疾病中的潜在作用已成为阐明MIF的生理和病理作用以及探索其在中枢神经系统疾病治疗中的潜在意义的研究重点。此前，大多数关于MIF功能调节的研究都集中在MIF互变异构酶抑制剂上。然而，越来越多的信息表明，MIF的功能远远超出其互变异构酶活性。在此，我们综述了在理解MIF在中枢神经系统疾病发病机制中的复杂作用以及针对MIF互变异构酶和核酸酶的小分子的发现与设计方面的最新进展。
