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Current Neuropharmacology

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ISSN (Print): 1570-159X
ISSN (Online): 1875-6190

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Research Article

Ameliorating Alzheimer’s-like Pathology by Minocycline via Inhibiting Cdk5/p25 Signaling

Author(s): Yu Zhao*, Chuanling Wang, Wenbo He and Zhiyou Cai*

Volume 20, Issue 9, 2022

Published on: 31 March, 2022

Page: [1783 - 1792] Pages: 10

DOI: 10.2174/1570159X19666211202124925

Price: $65

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 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 an 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), and biomarkers of synapse and Cdk5/p25 signaling, were detected by the Western blotting. The biomarkers of the 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. It limited the production of Aβ and hyperphosphorylation of tau in the hippocampus and ameliorated synaptic deficit. Moreover, it also inhibited the activation of Cdk5/p25 signaling, inflammation, and matrix metalloproteinases.

Conclusion: Minocycline mitigates Alzheimer’s-like pathology via limiting the activation of Cdk5/p25 signaling pathway and improves cognitive deficits

Keywords: Minocycline, Alzheimer’s disease, pathology, synapse, cyclin-dependent kinase 5, anti-inflammatory drugs.

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