Parkin overexpression ameliorates hippocampal long-term potentiation and β-amyloid load in an Alzheimer's disease mouse model
Parkin overexpression ameliorates hippocampal long-term potentiation and β-amyloid load in an Alzheimer's disease mouse model
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DOI：
10.1093/hmg/ddt501
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发表时间：
2014-02-15
影响因子：
3.5
通讯作者：
Huang, Fang
中科院分区：
文献类型：
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作者：
Hong, Xiaoqi;Liu, Jie;Huang, Fang
阿尔茨海默病（AD）是一种进行性神经退行性疾病，其特征是记忆能力严重下降。APPswe/PSEN1E9（APP/PS1）品系是一种被广泛研究的阿尔茨海默病小鼠模型，因为小鼠会出现淀粉样斑块以及记忆能力受损的情况。为了测试通过帕金蛋白恢复突触可塑性并减少β -淀粉样蛋白负荷是否可作为阿尔茨海默病的一个潜在治疗靶点，我们将APP/PS1转基因小鼠与过表达泛素连接酶帕金蛋白的转基因小鼠进行杂交，并分析后代的特性。在APP/PS1转基因小鼠中过表达帕金蛋白恢复了依赖活动的突触可塑性，并挽救了行为异常。此外，帕金蛋白的过表达与APP蛋白表达的下调、β -淀粉样蛋白负荷的减少以及炎症的减轻相关。我们的数据表明，帕金蛋白可能是阿尔茨海默病治疗的一个有前景的靶点。
Alzheimers disease (AD) is a progressive neurodegenerative disorder characterized by a severe decline of memory performance. A widely studied AD mouse model is the APPswe/PSEN1E9 (APP/PS1) strain, as mice exhibit amyloid plaques as well as impaired memory capacities. To test whether restoring synaptic plasticity and decreasing -amyloid load by Parkin could represent a potential therapeutic target for AD, we crossed APP/PS1 transgenic mice with transgenic mice overexpressing the ubiquitin ligase Parkin and analyzed offspring properties. Overexpression of Parkin in APP/PS1 transgenic mice restored activity-dependent synaptic plasticity and rescued behavioral abnormalities. Moreover, overexpression of Parkin was associated with down-regulation of APP protein expression, decreased -amyloid load and reduced inflammation. Our data suggest that Parkin could be a promising target for AD therapy.