Department of Neurology, Inovation Center for Neurological Disorders, Xuan Wu Hospital, Capital Medical University, Beijing, P.R. China.
Beijing Key Laboratory of Geriatric Cognitive Disorders, Beijing, P.R. China.
J Alzheimers Dis. 2018;62(4):1803-1813. doi: 10.3233/JAD-171110.
Abnormal amyloid-β (Aβ) aggregates are a striking feature of Alzheimer's disease (AD), and Aβ oligomers have been proven to be crucial in the pathology of AD. Any intervention targeting the generation or aggregation of Aβ can be expected to be useful in AD treatment. Oxidative stress and inflammation are common pathological changes in AD that are involved in the generation and aggregation of Aβ. In the present study, 6-month-old PS1V97L transgenic (Tg) mice were treated with sulforaphane, an antioxidant, for 4 months, and this treatment significantly inhibited the generation and aggregation of Aβ. Sulforaphane also alleviated several downstream pathological changes that including tau hyperphosphorylation, oxidative stress, and neuroinflammation. Most importantly, the cognition of the sulforaphane-treated PS1V97L Tg mice remained normal compared to that of wild-type mice at 10 months of age, when dementia typically emerges in PS1V97L Tg mice. Pretreating cultured cortical neurons with sulforaphane also protected against neuronal injury caused by Aβ oligomers in vitro. These findings suggest that sulforaphane may be a potential compound that can inhibit Aβ oligomer production in AD.
异常的淀粉样蛋白-β (Aβ) 聚集体是阿尔茨海默病 (AD) 的一个显著特征，Aβ 低聚物已被证明在 AD 的病理学中至关重要。任何针对 Aβ 产生或聚集的干预措施都有望对 AD 的治疗有用。氧化应激和炎症是 AD 的常见病理变化，涉及 Aβ 的产生和聚集。在本研究中，用抗氧化剂萝卜硫素处理 6 个月大的 PS1V97L 转基因 (Tg) 小鼠 4 个月，该治疗显著抑制了 Aβ 的产生和聚集。萝卜硫素还缓解了几种下游的病理变化，包括 tau 过度磷酸化、氧化应激和神经炎症。最重要的是，与 10 个月大时通常出现在 PS1V97L Tg 小鼠中的痴呆症相比，用萝卜硫素处理的 PS1V97L Tg 小鼠的认知能力保持正常。用萝卜硫素预处理培养的皮质神经元也可防止体外 Aβ 低聚物引起的神经元损伤。这些发现表明，萝卜硫素可能是一种潜在的化合物，可以抑制 AD 中的 Aβ 低聚物产生。
