miR-204-3p/Nox4 Mediates Memory Deficits in a Mouse Model of Alzheimer's Disease.

miR-204-3p/Nox4 Mediates Memory Deficits in a Mouse Model of Alzheimer's Disease.
复制标题

DOI：
10.1016/j.ymthe.2020.09.006
复制
发表时间：
2020-09
期刊：
Molecular therapy : the journal of the American Society of Gene Therapy
影响因子：
--
通讯作者：
Wenyuan Tao;Lin-jie Yu;Shu Shu-Shu;Y. Liu;Zi Zhuang;Si-yi Xu;Xin-yu Bao;Yue Gu;Fang Cai;
Wenyuan Tao;Lin-jie Yu;Shu Shu-Shu;Y. Liu;Zi Zhuang;Si-yi Xu;Xin-yu Bao;Yue Gu;Fang Cai;
中科院分区：
其他
文献类型：
--
作者：
Wenyuan Tao;Lin-jie Yu;Shu Shu-Shu;Y. Liu;Zi Zhuang;Si-yi Xu;Xin-yu Bao;Yue Gu;Fang Cai;

文献摘要

相似文献

阿尔茨海默病（Alzheimer's disease， AD）是老年人最常见的导致痴呆的神经退行性疾病，其发病机制尚未完全明确。MicroRNAs （miRNAs）已被证明与AD患者的记忆缺陷有关。在本研究中，我们发现6月龄APPswe/PS1dE9 （APP/PS1）小鼠海马和血浆中miR-204-3p下调。miR-204-3p过表达可减弱APP/PS1小鼠的记忆和突触缺陷。过表达miR-204-3p后，APP/PS1小鼠海马中淀粉样蛋白水平和氧化应激降低。烟酰胺腺嘌呤二核苷酸磷酸（NADPH）氧化酶4 （Nox4）是miR-204-3p的靶点，GLX351322抑制Nox4可以保护神经元细胞免受a β1 - 42诱导的神经毒性。此外，GLX351322治疗可挽救APP/PS1小鼠的突触和记忆缺陷，并降低海马中的氧化应激和淀粉样蛋白水平。这些结果表明，miR-204-3p通过靶向Nox4减轻APP/PS1小鼠的记忆缺陷和氧化应激，miR-204-3p过表达和/或Nox4抑制可能是治疗AD的潜在治疗策略。
Alzheimer's disease (AD) is the most common neurodegenerative disorder leading to dementia in the elderly, and the mechanisms of AD are not fully defined. MicroRNAs (miRNAs) have been shown to contribute to memory deficits in AD. In this study, we identified that miR-204-3p was downregulated in the hippocampus and plasma of 6-month-old APPswe/PS1dE9 (APP/PS1) mice. miR-204-3p overexpression attenuated memory and synaptic deficits in APP/PS1 mice. The amyloid levels and oxidative stress were decreased in the hippocampus of APP/PS1 mice after miR-204-3p overexpression. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 4 (Nox4) was a target of miR-204-3p, and Nox4 inhibition by GLX351322 protected neuronal cells against Aβ1–42-induced neurotoxicity. Furthermore, GLX351322 treatment rescued synaptic and memory deficits, and decreased oxidative stress and amyloid levels in the hippocampus of APP/PS1 mice. These results revealed that miR-204-3p attenuated memory deficits and oxidative stress in APP/PS1 mice by targeting Nox4, and miR-204-3p overexpression and/or Nox4 inhibition might be a potential therapeutic strategy for AD treatment.