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Current Alzheimer Research

Editor-in-Chief

ISSN (Print): 1567-2050
ISSN (Online): 1875-5828

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

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

Volume 13, Issue 6, 2016

Page: [663 - 677] Pages: 15

DOI: 10.2174/1567205013666160208142456

open access plus

Abstract

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.

Keywords: Alzheimer’s Disease, amyloid-β, blood-brain barrier, intracellular amyloid-β, neuronal loss, triphenylmethane dye.


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