Inhibition of interleukin-1ß plays a protective role in Alzheimer's disease by promoting microRNA-9-5p and downregulating targeting protein for xenopus kinesin-like protein 2.

ABSTRACT

OBJECTIVE: Evidences have indicated that interleukin-1ß (IL-1ß) and microRNAs (miRNAs) are implicated in Alzheimer's disease (AD), and we aimed to study the role of IL-1ß in AD development with the involvement of miR-9-5p and targeting protein for xenopus kinesin-like protein 2 (TPX2). METHODS: APPswe/PS1dE9 double transgenic mice and C57BL/6 wild type mice were treated with inhibited IL-1ß, miR-9-5p mimic and/or silenced TPX2. Expression of IL-1ß, miR-9-5p, TPX2, amyloid-ß (Aß) and p-tau in mouse hippocampal tissues was determined. The behavioral changes, hippocampal pathological injury, Aß plaque deposition, tau expression, neuronal apoptosis and oxidative stress of AD mice were all measured. The regulatory relationships between IL and 1ß and miR-9-5p, and between miR-9-5p and TPX2 were confirmed. RESULTS: IL-1ß and TPX2 were upregulated while miR-9-5p was downregulated in hippocampal tissues from AD mice versus non-transgenic littermate mice. Inhibited IL-1ß or elevated miR-9-5p improved behavioral changes and neuronal injury of AD mice, and suppressed plaque deposition and oxidative stress in hippocampal tissues of AD mice. These changes that induced by elevated miR-9-5p could be reversed by overexpression of TPX2. IL-1ß negatively regulated miR-9-5p, and TPX2 was a target gene of miR-9-5p. CONCLUSION: This study suggested that inhibition of IL-1ß played a protective role in AD by promoting miR-9-5p and downregulating TPX2, which may contribute to exploration on AD treatment.