Department of Pharmacology, College of Medicine, National Creative Research Initiative Center for Alzheimer's Dementia and Neuroscience Research Institute, MRC, Seoul National University, Seoul, South Korea.
Neurodegener Dis. 2012;10(1-4):27-9. doi: 10.1159/000333781. Epub 2012 Feb 1.
Neuroinflammation is one of the important pathogenic features of Alzheimer's disease (AD). Recently, S100a9 was found to be increased within neuritic plaques and reactive glia and was proposed to participate in the inflammation associated with the pathogenesis of AD. Our study showed that S100a9 expression was increased in the brains of AD mice and AD patients. In Tg2576 mice, knockdown by short hairpin RNA or knockout of the S100a9 gene significantly reduced the neuropathology, greatly improved the learning and memory impairment and reduced the amount of Aβ and APP-CTs by increasing neprilysin and decreasing BACE activity. These results clearly show that the upregulation of the S100a9 gene plays an important role in the neuropathology and memory impairment in AD, suggesting that the knockdown and knockout of this gene have a great therapeutic potential for AD.
神经炎症是阿尔茨海默病（AD）的重要发病特征之一。最近发现 S100a9 在神经纤维缠结和反应性胶质细胞中增加，并被提出参与与 AD 发病机制相关的炎症。我们的研究表明 S100a9 在 AD 小鼠和 AD 患者的大脑中表达增加。在 Tg2576 小鼠中，短发夹 RNA 敲低或 S100a9 基因敲除显著减少神经病理学，通过增加神经肽酶和降低 BACE 活性，大大改善学习和记忆障碍，并减少 Aβ 和 APP-CTs 的量。这些结果清楚地表明 S100a9 基因的上调在 AD 的神经病理学和记忆障碍中起着重要作用，表明该基因的敲低和敲除对 AD 具有很大的治疗潜力。
