Department of Neurology, Shenzhen Third People's Hospital, The Second Affiliated Hospital, Southern University of Science and Technology, Shenzhen, 518112, Guangdong, China.
Department of Neurology, Chongqing General Hospital, University of Chinese Academy of Sciences, Chongqing, 400013, Chongqing, China.
Curr Neuropharmacol. 2022 Aug 3;20(9):1783-1792. doi: 10.2174/1570159X19666211202124925.
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.
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.
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.
Minocycline mitigates Alzheimer's-like pathology via limiting the activation of Cdk5/p25 signaling pathway and improves cognitive deficits.
米诺环素在许多脑部疾病中具有多种神经保护作用，包括预防和治疗阿尔茨海默病（AD）。Cdk5/p25 信号在阿尔茨海默病样病理的发生和发展中起重要作用。本工作旨在进一步探讨米诺环素对与阿尔茨海默病样病理相关的 Cdk5/p25 信号的潜在机制。
通过 Morris 水迷宫试验测量动物的认知功能。通过酶联免疫吸附试验测定 Aβ 水平。通过 Western blot 检测 APP、β-和 γ- 分泌酶以及tau（总 tau 和磷酸化 tau）、炎症细胞因子和基质金属蛋白酶（MMP-2 和 MMP-9）的生物标志物，以及突触和 Cdk5/p25 信号的生物标志物。通过免疫荧光法测定突触、炎症细胞因子和基质金属蛋白酶（MMP-2 和 MMP-9）的生物标志物。
米诺环素改善了 APP/PS1 小鼠的学习和记忆。它限制了海马体中 Aβ 的产生和 tau 的过度磷酸化，并改善了突触缺陷。此外，它还抑制了 Cdk5/p25 信号通路的激活、炎症和基质金属蛋白酶。
米诺环素通过限制 Cdk5/p25 信号通路的激活减轻了阿尔茨海默病样病理，并改善了认知缺陷。
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