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Potential Retinoid X Receptor Agonists for Treating Alzheimer's Disease from Traditional Chinese Medicine

Alzheimer's disease is neurodegenerative disorder due to the accumulation of amyloid-β in the brain and causes dementia with ageing. Some researches indicate that the RXR agonist, Targretin, has also been used for treatment of Alzheimer's disease in mouse models. We investigate the potent...

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Autores principales: Chen, Kuan-Chung, Liu, Yu-Cheng, Lee, Cheng-Chun, Chen, Calvin Yu-Chian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi Publishing Corporation 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4021742/
https://www.ncbi.nlm.nih.gov/pubmed/24876869
http://dx.doi.org/10.1155/2014/278493
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author Chen, Kuan-Chung
Liu, Yu-Cheng
Lee, Cheng-Chun
Chen, Calvin Yu-Chian
author_facet Chen, Kuan-Chung
Liu, Yu-Cheng
Lee, Cheng-Chun
Chen, Calvin Yu-Chian
author_sort Chen, Kuan-Chung
collection PubMed
description Alzheimer's disease is neurodegenerative disorder due to the accumulation of amyloid-β in the brain and causes dementia with ageing. Some researches indicate that the RXR agonist, Targretin, has also been used for treatment of Alzheimer's disease in mouse models. We investigate the potent candidates as RXR agonists from the vast repertoire of TCM compounds in TCM Database@Taiwan. The potential TCM compounds, β-lipoic acid and sulfanilic acid, had higher potent binding affinities than both 9-cis-retinoic acid and Targretin in docking simulation and have stable H-bonds with residues Arg316 and some equivalent hydrophobic contacts with residues Ala272, Gln275, Leu309, Phe313, Val342, Ile345, and Cys432 as Targretin. The carboxyl or sulfonyl hydroxide group can form a H-bond with key residue Arg316 in the docking pose, and the phenyl group next to the carboxyl or sulfonyl hydroxide group can form a π interaction with residue Phe313. Moreover, β-lipoic acid and sulfanilic acid have stable H-bonds with residue Gln275, Ser313, and residue Ala327, respectively, which may strengthen and stabilize TCM candidates inside the binding domain of RXR protein. Hence, we propose β-lipoic acid and sulfanilic acid as potential lead compounds for further study in drug development process with the RXR protein against Alzheimer's disease.
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spelling pubmed-40217422014-05-29 Potential Retinoid X Receptor Agonists for Treating Alzheimer's Disease from Traditional Chinese Medicine Chen, Kuan-Chung Liu, Yu-Cheng Lee, Cheng-Chun Chen, Calvin Yu-Chian Evid Based Complement Alternat Med Research Article Alzheimer's disease is neurodegenerative disorder due to the accumulation of amyloid-β in the brain and causes dementia with ageing. Some researches indicate that the RXR agonist, Targretin, has also been used for treatment of Alzheimer's disease in mouse models. We investigate the potent candidates as RXR agonists from the vast repertoire of TCM compounds in TCM Database@Taiwan. The potential TCM compounds, β-lipoic acid and sulfanilic acid, had higher potent binding affinities than both 9-cis-retinoic acid and Targretin in docking simulation and have stable H-bonds with residues Arg316 and some equivalent hydrophobic contacts with residues Ala272, Gln275, Leu309, Phe313, Val342, Ile345, and Cys432 as Targretin. The carboxyl or sulfonyl hydroxide group can form a H-bond with key residue Arg316 in the docking pose, and the phenyl group next to the carboxyl or sulfonyl hydroxide group can form a π interaction with residue Phe313. Moreover, β-lipoic acid and sulfanilic acid have stable H-bonds with residue Gln275, Ser313, and residue Ala327, respectively, which may strengthen and stabilize TCM candidates inside the binding domain of RXR protein. Hence, we propose β-lipoic acid and sulfanilic acid as potential lead compounds for further study in drug development process with the RXR protein against Alzheimer's disease. Hindawi Publishing Corporation 2014 2014-04-30 /pmc/articles/PMC4021742/ /pubmed/24876869 http://dx.doi.org/10.1155/2014/278493 Text en Copyright © 2014 Kuan-Chung Chen et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Chen, Kuan-Chung
Liu, Yu-Cheng
Lee, Cheng-Chun
Chen, Calvin Yu-Chian
Potential Retinoid X Receptor Agonists for Treating Alzheimer's Disease from Traditional Chinese Medicine
title Potential Retinoid X Receptor Agonists for Treating Alzheimer's Disease from Traditional Chinese Medicine
title_full Potential Retinoid X Receptor Agonists for Treating Alzheimer's Disease from Traditional Chinese Medicine
title_fullStr Potential Retinoid X Receptor Agonists for Treating Alzheimer's Disease from Traditional Chinese Medicine
title_full_unstemmed Potential Retinoid X Receptor Agonists for Treating Alzheimer's Disease from Traditional Chinese Medicine
title_short Potential Retinoid X Receptor Agonists for Treating Alzheimer's Disease from Traditional Chinese Medicine
title_sort potential retinoid x receptor agonists for treating alzheimer's disease from traditional chinese medicine
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4021742/
https://www.ncbi.nlm.nih.gov/pubmed/24876869
http://dx.doi.org/10.1155/2014/278493
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