Ameliorating Alzheimer’s-like pathology by Minocycline via inhibiting Cdk5/p25 signaling

Abstract

Background: Minocycline has multiple neuroprotective roles in abundant brain diseases, including the prevention and treatment of Alzheimer’s disease (AD). Cdk5/p25 signaling plays an important role in the onset and development of Alzheimer’s-like pathology. The aim of the present work was to further explore the underlying mechanism which minocycline effects on Cdk5/p25 signaling related to the Alzheimer’s-like pathology. Methods: The cognitive function of animals was measured by the Morris water maze test. The levels of Aβ were determined by enzyme-linked immunosorbent assay. The levels of APP, β- and γ-secretases; and the biomarkers of tau (total tau and hyperphosphorylated tau), inflammatory cytokine and matrix metalloproteinases (MMP-2 and MMP-9), biomarkers of synapse and Cdk5/p25 signaling were detected by Western blotting. The biomarkers of synapse, inflammatory cytokine and matrix metalloproteinases (MMP-2 and MMP-9) were also determined by immunofluorescence. Results: Minocycline improved learning and memory in APP/PS1 mice. Minocycline limits the production of Aβ and hyperphosphorylation of tau in the hippocampus, and ameliorates synaptic deficit while minocycline inhibits the activation of Cdk5/p25 signaling, inflammation and activation of matrix metalloproteinases. Conclusion: Minocycline mitigates Alzheimer’s-like pathology via limiting the activation of Cdk5/p25 signaling pathway and improves cognitive deficits.