Background: The relationship between diabetes mellitus and neurodegenerative disorders has been of great interest. Macrophage migration inhibitory factor (MIF) is a pro-inflammatory cytokine in which a variety of signaling cascades are activated through it. MIF has been involved in the pathogenesis of several diseases and can predict early pre-symptomatic stages of neurodegeneration in diabetic patients.
Objective: To investigate whether serum MIF could predict brain neurodegeneration at the early pre-symptomatic stages in diabetic patients.
Methods: We examined adults with type 2 diabetes mellitus and compared with normal control adults using a short form of the IQCODE and biochemical examination, including assessment of HA1C, fasting blood glucose, lipid profile, and MIF which was measured by ELISA technique. Correlations between parameters were studied. Computational PathLinker bioinformatic tool was used to search for potential pathway reconstructions for the insulin/amyloid-β/MIF signaling.
Results: We demonstrated that MIF level was increased in the serum at the early pre-symptomatic stages of neurodegenerative disorder in diabetic patients. In addition, network analysis demonstrates that insulin receptor substrate 1 can ameliorate amyloid-β protein precursor through COP9 signalosome complex subunit 5 that enhances MIF elevation.
Conclusion: Diagnosis processes could not be used as routine examinations for still pre-symptomatic neurodegenerative disorders. This may be due to the time constraints and the heavy dependence on the physician's experience. Therefore, serum MIF level could predict brain neurodegeneration at the early pre-symptomatic stages in diabetic patients which may support its potential utility as a clinically useful biomarker.
Keywords: Biological network; IQCODE; PathLinker; macrophage migration inhibitory factor; neurodegenerative disorder; pre-symptomatic stages.