College of Life Sciences and Oceanography, Shenzhen University, Shenzhen, China; Department of Chemistry, Faculty of Science, Hong Kong Baptist University, Hong Kong, China.
Department of Chemistry, Faculty of Science, Hong Kong Baptist University, Hong Kong, China.
Exp Neurol. 2020 May;327:113210. doi: 10.1016/j.expneurol.2020.113210. Epub 2020 Jan 24.
Accumulation of β-amyloid (Aβ) peptide and hyperphosphorylated tau in the brain is one of the pathological characteristics of Alzheimer's disease (AD) and attractive therapeutic targets in its treatment. In the present study, the cognitive ability of 4-month-old 3 × Tg-AD mice significantly improved after 40 days treatment with intraperitoneal injection of 2.25 mg/kg of SLOH, which is a multifunctional carbazole-based cyanine fluorophore. It reduced Aβ deposition, tau levels and its hyperphosphorylation by modulating AKT and promoting protein phosphatase 2A activity in the brain as well as in the primary neurons of 3 × Tg-AD mice. Moreover, SLOH attenuated synaptic deficit both in vitro and in vivo by regulating the Ca/CaMKII/CREB signaling pathway. These findings strongly suggest that SLOH owns a high therapeutic potential to treat early onset AD.
β-淀粉样蛋白（Aβ）肽和过度磷酸化的 tau 在大脑中的积累是阿尔茨海默病（AD）的病理特征之一，也是其治疗的有吸引力的治疗靶点。在本研究中，腹腔注射 2.25mg/kg 的 SLOH（一种多功能咔唑基菁荧光染料）治疗 40 天后，3×Tg-AD 小鼠的认知能力显著提高。SLOH 通过调节 AKT 和促进大脑和 3×Tg-AD 小鼠原代神经元中的蛋白磷酸酶 2A 活性来减少 Aβ 沉积、tau 水平及其过度磷酸化。此外，SLOH 通过调节 Ca/CaMKII/CREB 信号通路来减轻体外和体内的突触缺陷。这些发现强烈表明，SLOH 具有治疗早发性 AD 的高治疗潜力。
