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Oral Triphenylmethane Food Dye Analog, Brilliant Blue G, Prevents Neuronal Loss in APPSwDI/NOS2-/- Mouse Model.
Curr Alzheimer Res 2016; 13(6):663-77CA

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.

Authors+Show Affiliations

No affiliation info available102 Gilmer Hall, PO Box 400400, Department of Psychology, University of Virginia, Charlottesville, Virginia 22904, USA. erisir@virginia.edu.School of Materials Science and Engineering, Gwangju Institute of Science and Technology, 123 Cheomdan-gwagiro, Buk-gu, Gwangju 61005, Republic of Korea. inchan@gist.ac.kr.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

Language

eng

PubMed ID

26852943

Citation

Irwin, Jacob A., et al. "Oral Triphenylmethane Food Dye Analog, Brilliant Blue G, Prevents Neuronal Loss in APPSwDI/NOS2-/- Mouse Model." Current Alzheimer Research, vol. 13, no. 6, 2016, pp. 663-77.
Irwin JA, Erisir A, Kwon I. Oral Triphenylmethane Food Dye Analog, Brilliant Blue G, Prevents Neuronal Loss in APPSwDI/NOS2-/- Mouse Model. Curr Alzheimer Res. 2016;13(6):663-77.
Irwin, J. A., Erisir, A., & Kwon, I. (2016). Oral Triphenylmethane Food Dye Analog, Brilliant Blue G, Prevents Neuronal Loss in APPSwDI/NOS2-/- Mouse Model. Current Alzheimer Research, 13(6), pp. 663-77.
Irwin JA, Erisir A, Kwon I. Oral Triphenylmethane Food Dye Analog, Brilliant Blue G, Prevents Neuronal Loss in APPSwDI/NOS2-/- Mouse Model. Curr Alzheimer Res. 2016;13(6):663-77. PubMed PMID: 26852943.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Oral Triphenylmethane Food Dye Analog, Brilliant Blue G, Prevents Neuronal Loss in APPSwDI/NOS2-/- Mouse Model. AU - Irwin,Jacob A, AU - Erisir,Alev, AU - Kwon,Inchan, PY - 2015/11/25/received PY - 2016/01/20/accepted PY - 2016/2/9/entrez PY - 2016/2/9/pubmed PY - 2017/1/4/medline SP - 663 EP - 77 JF - Current Alzheimer research JO - Curr Alzheimer Res VL - 13 IS - 6 N2 - 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. SN - 1875-5828 UR - https://www.unboundmedicine.com/medline/citation/26852943/Oral_Triphenylmethane_Food_Dye_Analog_Brilliant_Blue_G_Prevents_Neuronal_Loss_in_APPSwDI/NOS2_/__Mouse_Model_ L2 - http://www.eurekaselect.com/139303/article DB - PRIME DP - Unbound Medicine ER -