The Role of Macrophage Migration Inhibitory Factor in Alzheimer’s Disease

Abstract

Previous studies have shown that amyloid β protein (Aβ), the essential molecule for the formation of toxic oligomers and, subsequently, Alzheimer plaques, has been associated in vivo with the immune modulator, macrophage migration inhibitory factor (MIF) (17). To further investigate this association in vivo we used the APP transgenic mouse model. Serial brain sections of transgenic APP mice were stained for Aβ plaques and MIF and we observed MIF immunolabeling in microglial cells in association with Aβ plaques in the transgenic mouse brain sections. In addition, functional studies in murine and human neuronal cell lines revealed that Aβ-induced toxicity could be reversed significantly by a small molecule inhibitor of MIF (ISO-1). Finally, to elucidate the role of MIF in Alzheimer's Disease (AD) we measured MIF levels in the brain cytosol and cerebrospinal fluid (CSF) of AD patients and age-matched controls. Our results demonstrate a marked increase of MIF levels within the CSF of AD patients compared with controls. Combined, our results indicate a strong role for MIF in the pathogenesis of AD and furthermore suggest that inhibition of MIF may provide a valuable avenue of investigation for the prevention of disease onset, progression and/or severity.

CXCL12 and CXCR4 in the Peripheral Blood of Patients with Parkinson’s Disease

“…It has the ability to induce neuroinflammation by activation of microglia, which produce proinflammatory cytokines. High expression of MIF has been detected in active MS lesions and cerebrospinal fluid of AD patients [29, 30]. Based on our results, we hypothesize that MIF may activate CXCR4 and induce inflammation and neurotoxicity in PD.…”

Quantitative proteomics reveals that PEA15 regulates astroglial Aβ phagocytosis in an Alzheimer's disease mouse model

“…Pancreatic triacylglycerol lipase (PNLIP), Acyl-CoA dehydrogenase (ACADS) and dihydrolipoamide branched-chain transacylase (Dbt) participate in lipid metabolism and they can generate acetyl CoA, the direct material of cholesterol, which promotes Aβ deposition [48]. Macrophage migration-inhibitory factor (MIF) was physically associated and co-localized with Aβ peptide [50]; MIF was substantially up-regulated in AD patients and related with Aβ-induced neurotoxicity [51], implying that MIF is a potential therapeutic target for AD.…”

Drug Repositioning for Alzheimer’s Disease Based on Systematic ‘omics’ Data Mining

“…MIF is the second top ranking anti-AD target that was previously found to be elevated in the CSF of AD patients [44, 45]. As a pro-inflammatory cytokine, MIF is essential for promoting microglial activation [46].…”