Recombinant DNA vaccine against neurite outgrowth inhibitors attenuates behavioral deficits and decreases Abeta in an Alzheimer's disease mouse model
Recombinant DNA vaccine against neurite outgrowth inhibitors attenuates behavioral deficits and decreases Abeta in an Alzheimer's disease mouse model
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DOI：
10.1016/j.neuropharm.2012.10.023
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发表时间：
2013-07
影响因子：
4.7
通讯作者：
Lingling Zhang;Quanhong Ma;Wulin Yang;Xiang-rong Qi;Zhigang Yao;Ying-chao Liu;Liang Liang-Liang;Xiang Wang;Chun-mei Ma;Lan Huang;Yanfeng Xu;Hua Zhu;Wei Deng;Ying-ying Gao;L. Ruan;Zhicheng Xiao;C. Qin
中科院分区：
文献类型：
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作者：
Lingling Zhang;Quanhong Ma;Wulin Yang;Xiang-rong Qi;Zhigang Yao;Ying-chao Liu;Liang Liang-Liang;Xiang Wang;Chun-mei Ma;Lan Huang;Yanfeng Xu;Hua Zhu;Wei Deng;Ying-ying Gao;L. Ruan;Zhicheng Xiao;C. Qin
阿尔茨海默病（AD）是一种慢性神经退行性疾病，其导致学习和记忆能力的进行性丧失，并最终导致痴呆。中枢神经系统中神经元的不可再生性导致与AD的各种行为和心理症状相关的基本病理变化。少突胶质细胞和髓鞘相关的轴突生长抑制剂（NOIs）往往会阻碍神经元的再生。我们设计了一种由NOIs多个特异性抑制结构域组成的重组DNA疫苗。疫苗接种诱导针对用DNA引发的牛痘病毒加强方案处理的小鼠血清中的特异性结构域的有效抗体。该疫苗减弱了小鼠大脑中的神经元变性，并保护模型小鼠免受行为缺陷的影响。疫苗接种还减少了共转基因小鼠脑中可溶性Aβ寡聚体和淀粉样蛋白斑块的形成。此外，APP/PS1共转基因小鼠脑中的星形胶质细胞增多也有所减轻。结果表明，使用髓鞘和少突胶质细胞相关NOIs的多个特异性结构域的免疫治疗可能是阿尔茨海默病和其他退行性中枢神经系统疾病的一种有前途的方法。
Alzheimer's disease (AD) is a chronic neurodegenerative disease that causes a progressive loss in learning and memory capabilities and eventually results in dementia. The non-renewable nature of neurons in the central nervous system leads to the basic pathological changes that are related to the various behavioral and psychological symptoms of AD. Oligodendrocyte- and myelin-related neurite outgrowth inhibitors (NOIs) tend to hinder the regeneration of neurons. We designed a recombinant DNA vaccine composed of multiple specific inhibitory domains of NOIs. Vaccination induced effective antibodies against the specific domains in the sera of mice treated with a DNA primed-vaccinia virus boost regimen. The vaccine attenuated neuronal degeneration in the mouse brain and protected the model mice from behavioral deficits. Vaccination also decreased the formation of soluble Aβ oligomer and amyloid plaques in the co-transgenic mice brain. What's more, astrocytosis in brains of APP/PS1 co-transgenic mice was also relieved. The results suggested that immunotherapy with multiple specific domains of myelin- and oligodendrocyte-related NOIs may be a promising approach for Alzheimer's disease and other degenerative central nervous system diseases.