Francesca Fernandez, Caitlin Aust, Sarah Lye, Robyn Griffiths Lyn
School of Behavioural and Health Sciences, Faculty of Health Sciences, Australian Catholic University, 1100 Nudgee Rd, Banyo, Queensland, 4014, Australia.
Centre for Genomics and Personalised Medicine, Genomics Research Centre, Queensland University of Technology, 60 Musk Avenue, Kelvin Grove, QLD, 4059, Australia.
Brain Behav Immun Health. 2022 Feb 24;21:100435. doi: 10.1016/j.bbih.2022.100435. eCollection 2022 May.
Despite the rise of Alzheimer's disease (AD) in an ageing population, no cure is currently available for this disorder. This study assessed the role of a natural compound, Antroquinonol, in modifying the progression of AD when administered at the start and/or before appearance of symptoms and when the disease was well established, in a transgenic animal model. Antroquinonol was administered daily for 8 weeks, in 11 week (early stage) and 9 month (late stage) male transgenic mice (3 times Transgenic mice PS1, APP, and tau, 3 Tg XAD) and their respective aged controls. Behavioural testing (including Elevated Plus Maze Watermaze, Recognition object testing and Y maze) was performed at the end of the drug administration. In addition AD biomarkers (Amyloid beta 42 (Aβ42), tau and phospho-tau levels), oxidative stress and inflammatory markers, were assessed in tested mice brains after their sacrifice at the end of the treatment. When administered before the start of symptoms at 11 weeks, Antroquinonol treatment at 34 mg/kg (D2) and more consistently at 75 mg/kg (D3), had a significant effect on reducing systemic inflammatory markers (Interleukin 1, IL-1β and TNF-α) and AD biomarker (Amyloid Beta 42, Aβ42 and tau) levels in the brain. The reduction of behavioural impairment reported for 3TgXAD mice was observed significantly for the D3 drug dose only and for all behavioural tests, when administered at 11 weeks. Similarly, beneficial effects of Antroquinonol (at higher dose D3) were noted in the transgenic mice in terms of AD biomarkers (tau and phosphorylated-tau), systemic inflammatory (IL-1β), brain anti-inflammatory (Nrf2) and oxidative (3-Nitrotyrosine, 3NT) markers. Improvement of memory impairment was also reported when Antroquinonol (D3) was administered at late stage (9 months). Since Antroquinonol has been used without adverse effects in previous successful clinical trials, this drug may offer a new avenue of treatment to modify AD development and progression.
尽管在老龄化人口中阿尔茨海默病（AD）的发病率有所上升，但目前尚无治愈该疾病的方法。本研究在转基因动物模型中评估了天然化合物antroquinonol在疾病开始时和/或症状出现前以及疾病已确诊时给药对改变AD病程的作用。在11周龄（早期）和9月龄（晚期）的雄性转基因小鼠（三倍转基因小鼠PS1、APP和tau，3Tg XAD）及其相应的老年对照小鼠中，每天给予antroquinonol，持续8周。在药物给药结束时进行行为测试（包括高架十字迷宫、水迷宫、识别物体测试和Y迷宫）。此外，在治疗结束后处死受试小鼠后，对其大脑中的AD生物标志物（淀粉样蛋白β42（Aβ42）、tau和磷酸化tau水平）、氧化应激和炎症标志物进行评估。在11周龄症状出现前给药时，34mg/kg（D2）的antroquinonol治疗，以及更持续的75mg/kg（D3）治疗，对降低全身炎症标志物（白细胞介素1，IL-1β和肿瘤坏死因子-α）和大脑中的AD生物标志物（淀粉样蛋白β42，Aβ42和tau）水平有显著作用。仅在11周龄给药时，仅D3药物剂量在所有行为测试中对3TgXAD小鼠报告的行为损伤减少有显著观察。同样，在转基因小鼠中，就AD生物标志物（tau和磷酸化tau）、全身炎症（IL-1β）、大脑抗炎（Nrf2）和氧化（3-硝基酪氨酸，3NT）标志物而言，观察到antroquinonol（较高剂量D3）的有益作用。当在晚期（9个月）给予antroquinonol（D3）时，也报告了记忆损伤的改善。由于antroquinonol在先前成功的临床试验中使用时没有不良反应，这种药物可能为改变AD的发展和进程提供一种新的治疗途径。
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