脂联素受体1的抑制促进记忆功能障碍和阿尔茨海默氏病样病理。,Scientific Reports

当前位置： X-MOL 学术 › Sci. Rep. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

脂联素受体1的抑制促进记忆功能障碍和阿尔茨海默氏病样病理。
Scientific Reports ( IF 3.8 ) Pub Date : 2017-Sep-29 , DOI: 10.1038/s41598-017-12632-9
Min Woo Kim , Noman bin Abid , Myeong Hoon Jo , Min Gi Jo , Gwang Ho Yoon , Myeong Ok Kim

最近关于神经退行性变的研究集中于中枢神经系统能量代谢功能障碍和蛋白病。脂联素（ADPN）是一种来自脂肪细胞的激素，在通过脂联素受体调节周围器官的胰岛素敏感性和葡萄糖稳态方面起着重要作用。尽管有越来越多的证据表明脂联素具有神经保护特性，但脂联素受体的潜在作用尚未阐明。在这里，使用基因疗法介导的shRNA抑制，我们发现脂联素受体1（AdipoR1）抑制可诱导神经变性以及代谢功能障碍。AdipoR1组合式小鼠表现出体重增加和血浆化学异常，并且在行为研究中也显示出空间学习和记忆障碍。而且，AdipoR1抑制导致神经变性表型，神经元标记NeuN的表达减少以及胱天蛋白酶3的表达和活性增加。此外，AD病理包括胰岛素信号功能障碍，异常蛋白聚集和神经炎性反应在AdipoR1敲除组中表现出高度一致性，这是一致的ADPN基因敲除小鼠的脑部疾病。总之，这些结果表明，ADPN-AdipoR1信号传导具有缓解神经退行性疾病（如阿尔茨海默氏病）的潜力。与ADPN基因敲除小鼠的脑部病理学一致。总之，这些结果表明，ADPN-AdipoR1信号传导具有缓解神经退行性疾病（如阿尔茨海默氏病）的潜力。与ADPN基因敲除小鼠的脑部病理学一致。总之，这些结果表明，ADPN-AdipoR1信号传导具有缓解神经退行性疾病（如阿尔茨海默氏病）的潜力。

"点击查看英文标题和摘要"

Suppression of adiponectin receptor 1 promotes memory dysfunction and Alzheimer's disease-like pathologies.

Recent studies on neurodegeneration have focused on dysfunction of CNS energy metabolism as well as proteinopathies. Adiponectin (ADPN), an adipocyte-derived hormone, plays a major role in the regulation of insulin sensitivity and glucose homeostasis in peripheral organs via adiponectin receptors. In spite of accumulating evidence that adiponectin has neuroprotective properties, the underlying role of adiponectin receptors has not been illuminated. Here, using gene therapy-mediated suppression with shRNA, we found that adiponectin receptor 1 (AdipoR1) suppression induces neurodegeneration as well as metabolic dysfunction. AdipoR1 knockdown mice exhibited increased body weight and abnormal plasma chemistry and also showed spatial learning and memory impairment in behavioural studies. Moreover, AdipoR1 suppression resulted in neurodegenerative phenotypes, diminished expression of the neuronal marker NeuN, and increased expression and activity of caspase 3. Furthermore, AD-like pathologies including insulin signalling dysfunction, abnormal protein aggregation and neuroinflammatory responses were highly exhibited in AdipoR1 knockdown groups, consistent with brain pathologies in ADPN knockout mice. Together, these results suggest that ADPN-AdipoR1 signalling has the potential to alleviate neurodegenerative diseases such as Alzheimer's diseases.

更新日期：2017-09-29

点击分享查看原文

点击收藏

公开下载

阅读更多本刊新发论文本刊介绍/投稿指南