Department of Neurology, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning, People's Republic of China.
Department of Anatomy, Foundation Institute of Jinzhou Medical University, Jinzhou, Liaoning, People's Republic of China.
J Mol Neurosci. 2019 Oct;69(2):246-253. doi: 10.1007/s12031-019-01353-5. Epub 2019 Jun 26.
Alzheimer's disease (AD) is the most common cause of dementia and is characterized by the presence of β-amyloid (Aβ) plaques and defective autophagy in the brain, which is believed to cause neuronal dysfunction. By using APP/PS1 transgenic AD mice, we investigated the influence of orientin (Ori) on cognitive function and its underlying mechanisms in AD models. Our data indicated that Ori improved spatial learning and memory in APP/PS1 mice, possibly through decreasing brain Aβ deposition and attenuating autophagy impairment. Ori decreased the LC3-II/I ratio, p62 and cathepsin D (Ctsd) protein levels and the number of autolysosomes, whereas the protein levels of Ulk1 and Beclin-1 were no different between the control and treatment groups, indicating increased autolysosome clearance and thus a decreased Aβ burden in the brain. Our results showed that Ori could enhance autolysosome clearance, decrease brain Aβ deposition and improve learning and memory in AD mice.
阿尔茨海默病（AD）是痴呆症最常见的病因，其特征是大脑中存在β-淀粉样蛋白（Aβ）斑块和自噬缺陷，这被认为会导致神经元功能障碍。通过使用 APP/PS1 转基因 AD 小鼠，我们研究了桃叶珊瑚苷（Ori）对 AD 模型中认知功能的影响及其潜在机制。我们的数据表明，Ori 可改善 APP/PS1 小鼠的空间学习和记忆能力，这可能是通过减少大脑 Aβ 沉积和减轻自噬损伤来实现的。Ori 降低了 LC3-II/I 比值、p62 和组织蛋白酶 D（Ctsd）蛋白水平以及自噬溶酶体的数量，而 Ulk1 和 Beclin-1 的蛋白水平在对照组和治疗组之间没有差异，这表明自噬溶酶体的清除增加，从而减少了大脑中的 Aβ 负担。我们的结果表明，Ori 可增强自噬溶酶体的清除，减少大脑中的 Aβ 沉积，并改善 AD 小鼠的学习和记忆能力。
