Mechanism of microRNA-22 in regulating neuroinflammation in Alzheimer's disease

Background: Study on the expression of miRNA-22 in serum of Alzheimer's disease (AD) patients and the mechanism of neuroinflammation regulation.

Methods: ELISA assay was used to detect the serum level of inflammatory factors, including interleukin-1β (IL-1β), interleukin-18 (IL-18), and tumor necrosis factor-α in AD patients. TargetScan database and luciferase reporter gene assay indicated that gasdermin D (GSDMD) was the target gene of miRNA-22. miRNA-22 mimic was transfected into microglia, followed by administration of LPS and Nigericin to induce pyroptosis.

Results: In this study, we found that the expression level of miRNA-22 in peripheral blood was lower in AD patients than that in healthy population. The expression of inflammatory factors was higher in AD patients than that in healthy people, which was negatively correlated with miRNA-22. miRNA-22 mimic could significantly inhibit pyroptosis, the expression of GSDMD and p30-GSDMD was down-regulated, the release of inflammatory factor was decreased, and the expression of NLRP3 inflammasome was down-regulated as feedback. In the APP/PS1 double transgenic mouse model, the injection of miRNA-22 mimic significantly improved the memory ability and behavior of mice. In addition, the expression of the vital protein of pyroptosis in mouse brain tissue, including GSDMD and p30-GSDMD, was down-regulated, and the expression of inflammatory factors was also decreased.

Conclusion: miRNA-22 was negatively correlated with the expression of inflammatory factors in AD patients, and miRNA-22 could inhibit the release of inflammatory cytokines by regulating the inflammatory pyroptosis of glial cells via targeting GSDMD, thereby improving cognitive ability in AD mice. miRNA-22 and pyroptosis are potential novel therapeutic targets in the treatment of AD.