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Oral Triphenylmethane Food Dye Analog, Brilliant Blue G, Prevents Neuronal Loss in APPSwDI/NOS2-/- Mouse Model
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 assa...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Bentham Science Publishers
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5441128/ https://www.ncbi.nlm.nih.gov/pubmed/26852943 http://dx.doi.org/10.2174/15672050136661602081424568 |
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author | Irwin, Jacob A. Erisir, Alev Kwon, Inchan |
author_facet | Irwin, Jacob A. Erisir, Alev Kwon, Inchan |
author_sort | Irwin, Jacob A. |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-5441128 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Bentham Science Publishers |
record_format | MEDLINE/PubMed |
spelling | pubmed-54411282017-06-05 Oral Triphenylmethane Food Dye Analog, Brilliant Blue G, Prevents
Neuronal Loss in APPSwDI/NOS2-/- Mouse Model Irwin, Jacob A. Erisir, Alev Kwon, Inchan Curr Alzheimer Res Article 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. Bentham Science Publishers 2016-06 2016-06 /pmc/articles/PMC5441128/ /pubmed/26852943 http://dx.doi.org/10.2174/15672050136661602081424568 Text en © 2016 Bentham Science Publishers https://creativecommons.org/licenses/by-nc/4.0/legalcode This is an open access article licensed under the terms of the Creative Commons Attribution-Non-Commercial 4.0 International Public License (CC BY-NC 4.0) (https://creativecommons.org/licenses/by-nc/4.0/legalcode), which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited. |
spellingShingle | Article Irwin, Jacob A. Erisir, Alev Kwon, Inchan Oral Triphenylmethane Food Dye Analog, Brilliant Blue G, Prevents Neuronal Loss in APPSwDI/NOS2-/- Mouse Model |
title | Oral Triphenylmethane Food Dye Analog, Brilliant Blue G, Prevents
Neuronal Loss in APPSwDI/NOS2-/- Mouse Model |
title_full | Oral Triphenylmethane Food Dye Analog, Brilliant Blue G, Prevents
Neuronal Loss in APPSwDI/NOS2-/- Mouse Model |
title_fullStr | Oral Triphenylmethane Food Dye Analog, Brilliant Blue G, Prevents
Neuronal Loss in APPSwDI/NOS2-/- Mouse Model |
title_full_unstemmed | Oral Triphenylmethane Food Dye Analog, Brilliant Blue G, Prevents
Neuronal Loss in APPSwDI/NOS2-/- Mouse Model |
title_short | Oral Triphenylmethane Food Dye Analog, Brilliant Blue G, Prevents
Neuronal Loss in APPSwDI/NOS2-/- Mouse Model |
title_sort | oral triphenylmethane food dye analog, brilliant blue g, prevents
neuronal loss in appswdi/nos2-/- mouse model |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5441128/ https://www.ncbi.nlm.nih.gov/pubmed/26852943 http://dx.doi.org/10.2174/15672050136661602081424568 |
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