Behavioral/systems/cognitive Selectively Silencing Gsk-3 Isoforms Reduces Plaques and Tangles in Mouse Models of Alzheimer's Disease
Behavioral/systems/cognitive Selectively Silencing Gsk-3 Isoforms Reduces Plaques and Tangles in Mouse Models of Alzheimer's Disease
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通讯作者：
David E Hurtado;L. Molina-Porcel;J. Carroll;C. Macdonald;A. K. Aboagye;J. Trojanowski;Virginia M;Y. Lee
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作者：
David E Hurtado;L. Molina-Porcel;J. Carroll;C. Macdonald;A. K. Aboagye;J. Trojanowski;Virginia M;Y. Lee
糖原合酶激酶-3（GSK-3）与阿尔茨海默病（AD）、老年斑（SP）和神经元缠结（NFT）的发病机制有关，但GSK-3 β和β亚型中的每一种对AD机制的具体贡献尚未阐明。在这项研究中，我们试图阐明每个GSK-3 β和GSK-3 β使用新的病毒和遗传方法的作用。首先，我们开发了重组腺相关病毒2/1短发夹RNA构建体，其特异性地降低GSK-3 β或GSK-3 β的表达和活性。将这些构建体脑室内注射到SP（PDAPP β/β）、SP和NFT（PDAPP β/β）的新生AD转基因（tg）小鼠模型中
Glycogen synthase kinase-3 (GSK-3) is linked to the pathogenesis of Alzheimer's disease (AD), senile plaques (SPs), and neurofibrillary tangles (NFTs), but the specific contributions of each of the GSK-3 ␣ and  isoforms to mechanisms of AD have not been clarified. In this study, we sought to elucidate the role of each GSK-3␣ and GSK-3 using novel viral and genetic approaches. First, we developed recombinant adeno-associated virus 2/1 short hairpin RNA constructs which specifically reduced expression and activity of GSK-3␣ or GSK-3. These constructs were injected intraventricularly in newborn AD transgenic (tg) mouse models of SPs (PDAPP ϩ/Ϫ), both SPs and NFTs (PDAPP ϩ/Ϫ