期刊
BMC NEUROSCIENCE
卷 9, 期 -, 页码 -出版社
BMC
DOI: 10.1186/1471-2202-9-109
关键词
-
资金
- NIH [AG18440, AG022074, AG10435]
Background: Proteolytic degradation has emerged as a key pathway involved in controlling levels of the Alzheimer's disease (AD)-associated amyloid-beta (A beta) peptide in the brain. The endopeptidase, neprilysin, has been implicated as a major A beta degrading enzyme in mice and humans. Previous short and intermediate term studies have shown the potential therapeutic application of neprilysin by delivering this enzyme into the brain of APP transgenic mice using gene transfer with viral vectors. However the effects of long-term neprilysin gene transfer on other aspects of A beta associated pathology have not been explored yet in APP transgenic mice. Results: We show that the sustained expression of neprilysin for up to 6 months lowered not only the amyloid plaque load but also reduced the levels of intracellular A beta immunoreactivity. This was associated with improved behavioral performance in the water maze and ameliorated the dendritic and synaptic pathology in the APP transgenic mice. Conclusion: These data support the possibility that long-term neprilysin gene therapy improves behavioral and neurodegenerative pathology by reducing intracellular A beta.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据