miR-135a-5p mediates memory and synaptic impairments via the Rock2/Adducin1 signaling pathway in a mouse model of Alzheimer's disease.
miR-135a-5p mediates memory and synaptic impairments via the Rock2/Adducin1 signaling pathway in a mouse model of Alzheimer's disease.
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在阿尔茨海默病小鼠模型中，miR-135a-5p 通过 Rock2/Adducin1 信号通路介导记忆和突触损伤
DOI：
10.1038/s41467-021-22196-y
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发表时间：
2021-03-26
影响因子：
16.6
通讯作者：
Zhu LQ
中科院分区：
文献类型：
--
作者：
Zheng K;Hu F;Zhou Y;Zhang J;Zheng J;Lai C;Xiong W;Cui K;Hu YZ;Han ZT;Zhang HH;Chen JG;Man HY;Liu D;Lu Y;Zhu LQ
微小RNA（microRNAs，miRNAs）的异常调控与阿尔茨海默病（Alzheimer's disease，AD）的发病机制有关，但AD中发现的大多数异常表达的miRNAs不受突触活动的调控。在这里，我们报告了miR-135 a-5 p/Rock 2/Add 1的功能障碍导致AD小鼠模型中的记忆/突触障碍。在AD模型小鼠的兴奋性海马神经元中，miR-135 a-5 p水平显著降低。这种减少是tau依赖性的，并由Foxd 3介导。miR-135 a-5 p的抑制导致突触障碍和记忆障碍。此外，由miR-135 a-5 p缺失引起的过量Rock 2水平通过内收蛋白1（Add 1）上Ser 726的磷酸化在AD的突触障碍中起重要作用。用膜渗透性肽阻断Add 1上Ser 726的磷酸化可以有效地挽救AD小鼠的记忆障碍。综上所述，这些发现表明，突触相关的miR-135 a-5 p通过Rock 2/Add 1信号通路介导AD中的突触/记忆缺陷，阐明了AD的潜在治疗策略。已经显示，在阿尔茨海默病个体的脑组织或血清中以及在AD小鼠模型中，几种微小RNA被失调。作者表明，miR-135 a-5 p在AD小鼠的兴奋性锥体神经元中下调，并且miR-135 a-5 p/Rock 2/Add 1的功能障碍导致AD中的记忆/突触障碍。
Aberrant regulation of microRNAs (miRNAs) has been implicated in the pathogenesis of Alzheimer’s disease (AD), but most abnormally expressed miRNAs found in AD are not regulated by synaptic activity. Here we report that dysfunction of miR-135a-5p/Rock2/Add1 results in memory/synaptic disorder in a mouse model of AD. miR-135a-5p levels are significantly reduced in excitatory hippocampal neurons of AD model mice. This decrease is tau dependent and mediated by Foxd3. Inhibition of miR-135a-5p leads to synaptic disorder and memory impairments. Furthermore, excess Rock2 levels caused by loss of miR-135a-5p plays an important role in the synaptic disorder of AD via phosphorylation of Ser726 on adducin 1 (Add1). Blocking the phosphorylation of Ser726 on Add1 with a membrane-permeable peptide effectively rescues the memory impairments in AD mice. Taken together, these findings demonstrate that synaptic-related miR-135a-5p mediates synaptic/memory deficits in AD via the Rock2/Add1 signaling pathway, illuminating a potential therapeutic strategy for AD. Several micro RNAs have been shown to be deregulated in brain tissue or sera from individuals with Alzheimer’s disease and in AD mouse models. The authors show that miR-135a-5p is downregulated in excitatory pyramidal neurons from AD mice and that dysfunction of miR-135a-5p/Rock2/Add1 results in memory/synaptic disorder in AD.
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影响因子：
16.2
作者：
Edbauer, Dieter;Neilson, Joel R.;Foster, Kelly A.;Wang, Chi-Fong;Seeburg, Daniel P.;Batterton, Matthew N.;Tada, Tomoko;Dolan, Bridget M.;Sharp, Phillip A.;Sheng, Morgan
通讯作者：
Sheng, Morgan
FOXD3/miR-214/MED19 轴抑制人结直肠癌的肿瘤生长和转移
影响因子：
8.8
作者：
He, G. Y.;Hu, J. L.;Zhou, L.;Zhu, X. H.;Xin, S. N.;Zhang, D.;Lu, G. F.;Liao, W. T.;Ding, Y. Q.;Liang, L.
通讯作者：
Liang, L.
影响因子：
11
作者：
Chopra N;Wang R;Maloney B;Nho K;Beck JS;Pourshafie N;Niculescu A;Saykin AJ;Rinaldi C;Counts SE;Lahiri DK
通讯作者：
Lahiri DK
大鼠可卡因诱导的条件性位置偏好的获得和消失过程中海马 microRNA 表达谱的变化，
影响因子：
11
作者：
Chen CL;Liu H;Guan X
通讯作者：
Guan X
DOI：
10.1073/pnas.1008200107
发表时间：
2010-09-21
影响因子：
11.1
作者：
Ge, Yuan;Dong, Zhifang;Wang, Yu Tian
通讯作者：
Wang, Yu Tian