Oral Triphenylmethane Food Dye Analog, Brilliant Blue G, Prevents Neuronal Loss in APPSwDI/NOS2-/- Mouse Model
Oral Triphenylmethane Food Dye Analog, Brilliant Blue G, Prevents Neuronal Loss in APPSwDI/NOS2-/- Mouse Model
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DOI：
10.2174/1567205013666160208142456
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发表时间：
2016-01-01
影响因子：
2.1
通讯作者：
Kwon, Inchan
中科院分区：
文献类型：
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作者：
Irwin, Jacob A.;Erisir, Alev;Kwon, Inchan
减少淀粉样蛋白 (Aβ) 积累是开发阿尔茨海默病 (AD) 疗法的一个有前景的策略。我们最近报道了一种三苯甲烷食用染料类似物亮蓝 G (BBG)，它是体外β-淀粉样蛋白聚集和细胞检测中细胞毒性的剂量依赖性调节剂。继最近的工作之后，我们试图在治疗相关的 AD 转基因小鼠模型中进一步评估这种新型调节剂。对 APPSwDI/NOS2-/- 小鼠口服 BBG 三个月，以评估其生物相容性、穿过血脑屏障的渗透性以及挽救 AD 病理的功效。结果表明，BBG 在 APPSwDI/NOS2-/- 小鼠中具有良好的耐受性，不会引起明显的体重变化/异常行为，并且能够显着穿过 AD 血脑屏障。脑切片的免疫组织化学和电子显微镜分析表明，BBG 能够显着防止海马神经元神经元丢失并减少细胞内 APP/A beta。这是第一份报告：1) 亮蓝 G 对 AD 转基因动物模型中神经元损失的影响，2) 口服 BBG 对蛋白质构象/聚集疾病的影响，以及 3) APPSwDI/NOS2-/-小鼠中 AD 病理学的电子显微镜超微结构分析。
Reducing amyloid-beta (A beta) accumulation is a promising strategy for developing Alzheimer's Disease (AD) therapeutics. We recently reported that a triphenylmethane food dye analog, Brilliant Blue G (BBG), is a dose-dependent modulator of in vitro amyloid-beta aggregation and cytotoxicity in cell-based assays. Following up on this recent work, we sought to further evaluate this novel modulator in a therapeutically-relevant AD transgenic mouse model. BBG was orally administered to APPSwDI/NOS2-/- mice for three months in order to assess its biocompatibility, its permeability across the blood-brain barrier, and its efficacy at rescuing AD pathology. The results showed that BBG was well-tolerated, caused no significant weight change/unusual behavior, and was able to significantly cross the AD blood-brain barrier in APPSwDI/NOS2-/-mice. Immunohistochemical and electron microscopic analysis of the brain sections revealed that BBG was able to significantly prevent neuronal loss and reduce intracellular APP/A beta in hippocampal neurons. This is the first report of 1) the effect of Brilliant Blue G on neuronal loss in a transgenic animal model of AD, 2) oral administration of BBG to affect a protein conformation/aggregation disease, and 3) electron microscopic ultrastructural analysis of AD pathology in APPSwDI/NOS2-/-mice.