口服三苯甲烷类食品染料类似物，亮蓝G，防止神经元丢失APPSwDI / NOS2 -/-小鼠模型

Title:Oral Triphenylmethane Food Dye Analog, Brilliant Blue G, Prevents Neuronal Loss in APPSwDI/NOS2-/- Mouse Model

Volume: 13 Issue: 6

Author(s): Jacob A. Irwin, Alev Erisir, Inchan Kwon

Affiliation:

关键词: 阿尔茨海默病，淀粉样-β，血脑屏障，细胞内淀粉样-β，神经元损失，三苯甲烷染料

摘要: Reducing amyloid-β (Aβ) 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-β 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/Aβ 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.

Cite this article as:

Jacob A. Irwin, Alev Erisir, Inchan Kwon , Oral Triphenylmethane Food Dye Analog, Brilliant Blue G, Prevents Neuronal Loss in APPSwDI/NOS2-/- Mouse Model, Current Alzheimer Research 2016; 13 (6) . https://dx.doi.org/10.2174/1567205013666160208142456