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A Systematic Strategy for Discovering a Therapeutic Drug for Alzheimer’s Disease and Its Target Molecule
Natural medicines are attractive sources of leading compounds that can be used as interventions for neurodegenerative disorders. The complexity of their chemical components and undetermined bio-metabolism have greatly hindered both the use of natural medicines and the identification of their active...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2017
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5474478/ https://www.ncbi.nlm.nih.gov/pubmed/28674493 http://dx.doi.org/10.3389/fphar.2017.00340 |
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author | Yang, Zhiyou Kuboyama, Tomoharu Tohda, Chihiro |
author_facet | Yang, Zhiyou Kuboyama, Tomoharu Tohda, Chihiro |
author_sort | Yang, Zhiyou |
collection | PubMed |
description | Natural medicines are attractive sources of leading compounds that can be used as interventions for neurodegenerative disorders. The complexity of their chemical components and undetermined bio-metabolism have greatly hindered both the use of natural medicines and the identification of their active constituents. Here, we report a systematic strategy for evaluating the bioactive candidates in natural medicines used for Alzheimer’s disease (AD). We found that Drynaria Rhizome could enhance memory function and ameliorate AD pathologies in 5XFAD mice. Biochemical analysis led to the identification of the bio-effective metabolites that are transferred to the brain, namely, naringenin and its glucuronides. To explore the mechanism of action, we combined the drug affinity responsive target stability with immunoprecipitation-liquid chromatography/mass spectrometry analysis, identifying the collapsin response mediator protein 2 protein as a target of naringenin. Our study indicates that biochemical analysis coupled with pharmacological methods can be used in the search for new targets for AD intervention. |
format | Online Article Text |
id | pubmed-5474478 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-54744782017-07-03 A Systematic Strategy for Discovering a Therapeutic Drug for Alzheimer’s Disease and Its Target Molecule Yang, Zhiyou Kuboyama, Tomoharu Tohda, Chihiro Front Pharmacol Pharmacology Natural medicines are attractive sources of leading compounds that can be used as interventions for neurodegenerative disorders. The complexity of their chemical components and undetermined bio-metabolism have greatly hindered both the use of natural medicines and the identification of their active constituents. Here, we report a systematic strategy for evaluating the bioactive candidates in natural medicines used for Alzheimer’s disease (AD). We found that Drynaria Rhizome could enhance memory function and ameliorate AD pathologies in 5XFAD mice. Biochemical analysis led to the identification of the bio-effective metabolites that are transferred to the brain, namely, naringenin and its glucuronides. To explore the mechanism of action, we combined the drug affinity responsive target stability with immunoprecipitation-liquid chromatography/mass spectrometry analysis, identifying the collapsin response mediator protein 2 protein as a target of naringenin. Our study indicates that biochemical analysis coupled with pharmacological methods can be used in the search for new targets for AD intervention. Frontiers Media S.A. 2017-06-19 /pmc/articles/PMC5474478/ /pubmed/28674493 http://dx.doi.org/10.3389/fphar.2017.00340 Text en Copyright © 2017 Yang, Kuboyama and Tohda. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Pharmacology Yang, Zhiyou Kuboyama, Tomoharu Tohda, Chihiro A Systematic Strategy for Discovering a Therapeutic Drug for Alzheimer’s Disease and Its Target Molecule |
title | A Systematic Strategy for Discovering a Therapeutic Drug for Alzheimer’s Disease and Its Target Molecule |
title_full | A Systematic Strategy for Discovering a Therapeutic Drug for Alzheimer’s Disease and Its Target Molecule |
title_fullStr | A Systematic Strategy for Discovering a Therapeutic Drug for Alzheimer’s Disease and Its Target Molecule |
title_full_unstemmed | A Systematic Strategy for Discovering a Therapeutic Drug for Alzheimer’s Disease and Its Target Molecule |
title_short | A Systematic Strategy for Discovering a Therapeutic Drug for Alzheimer’s Disease and Its Target Molecule |
title_sort | systematic strategy for discovering a therapeutic drug for alzheimer’s disease and its target molecule |
topic | Pharmacology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5474478/ https://www.ncbi.nlm.nih.gov/pubmed/28674493 http://dx.doi.org/10.3389/fphar.2017.00340 |
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