Global brain delivery of neprilysin gene by intravascular administration of AAV vector in mice.
Global brain delivery of neprilysin gene by intravascular administration of AAV vector in mice.
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DOI：
10.1038/srep01472
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发表时间：
2013
影响因子：
4.6
通讯作者：
Saido, Takaomi C.
中科院分区：
文献类型：
--
作者：
Iwata, Nobuhisa;Sekiguchi, Misaki;Hattori, Yoshino;Takahashi, Akane;Asai, Masashi;Ji, Bin;Higuchi, Makoto;Staufenbiel, Matthias;Muramatsu, Shin-ichi;Saido, Takaomi C.
脑内淀粉样β肽（Aβ）的蓄积与阿尔茨海默病（AD）的认知功能下降密切相关。已显示将脑啡肽酶编码病毒载体立体定位输注到海马中可降低AD模型小鼠中的Aβ，但需要更有效和全面的递送来治疗AD中广泛分布的负荷。在这里，我们开发了一种腺相关病毒（AAV）载体，能够提供神经元基因表达后，外周给药整个大脑。在AD模型小鼠中，单次心内给予携带脑啡肽酶基因的载体可广泛提高脑啡肽酶活性，并减少Aβ寡聚体，同时缓解异常学习和记忆功能，改善淀粉样蛋白负荷。外源性脑啡肽酶主要定位于核内体，从而有效地将Aβ寡聚体从脑中排除。AAV载体介导的基因转移可以为神经退行性疾病提供治疗策略，其中治疗基因到脑中的全局转导是必要的。
Accumulation of amyloid-β peptide (Aβ) in the brain is closely associated with cognitive decline in Alzheimer's disease (AD). Stereotaxic infusion of neprilysin-encoding viral vectors into the hippocampus has been shown to decrease Aβ in AD-model mice, but more efficient and global delivery is necessary to treat the broadly distributed burden in AD. Here we developed an adeno-associated virus (AAV) vector capable of providing neuronal gene expression throughout the brains after peripheral administration. A single intracardiac administration of the vector carrying neprilysin gene in AD-model mice elevated neprilysin activity broadly in the brain, and reduced Aβ oligomers, with concurrent alleviation of abnormal learning and memory function and improvement of amyloid burden. The exogenous neprilysin was localized mainly in endosomes, thereby effectively excluding Aβ oligomers from the brain. AAV vector-mediated gene transfer may provide a therapeutic strategy for neurodegenerative diseases, where global transduction of a therapeutic gene into the brain is necessary.
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DOI：
10.1523/jneurosci.2312-08.2008
发表时间：
2008-11-19
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Ji B;Maeda J;Sawada M;Ono M;Okauchi T;Inaji M;Zhang MR;Suzuki K;Ando K;Staufenbiel M;Trojanowski JQ;Lee VM;Higuchi M;Suhara T
通讯作者：
Suhara T
影响因子：
5.3
作者：
Nilsson P;Iwata N;Muramatsu S;Tjernberg LO;Winblad B;Saido TC
通讯作者：
Saido TC
影响因子：
12.4
作者：
Muramatsu, Shin-ichi;Fujimoto, Ken-ichi;Nakano, Imaharu
通讯作者：
Nakano, Imaharu
影响因子：
82.9
作者：
Iwata, N;Tsubuki, S;Saido, TC
通讯作者：
Saido, TC
影响因子：
3.5
作者：
Miyakawa, T;Yared, E;Crawley, JN
通讯作者：
Crawley, JN