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Literature-Based Discovery Predicts Antihistamines Are a Promising Repurposed Adjuvant Therapy for Parkinson’s Disease

Parkinson’s disease (PD) is a movement disorder caused by a dopamine deficit in the brain. Current therapies primarily focus on dopamine modulators or replacements, such as levodopa. Although dopamine replacement can help alleviate PD symptoms, therapies targeting the underlying neurodegenerative pr...

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Autores principales: Tandra, Gabriella, Yoone, Amy, Mathew, Rhea, Wang, Minzhi, Hales, Chadwick M., Mitchell, Cassie S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10418861/
https://www.ncbi.nlm.nih.gov/pubmed/37569714
http://dx.doi.org/10.3390/ijms241512339
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author Tandra, Gabriella
Yoone, Amy
Mathew, Rhea
Wang, Minzhi
Hales, Chadwick M.
Mitchell, Cassie S.
author_facet Tandra, Gabriella
Yoone, Amy
Mathew, Rhea
Wang, Minzhi
Hales, Chadwick M.
Mitchell, Cassie S.
author_sort Tandra, Gabriella
collection PubMed
description Parkinson’s disease (PD) is a movement disorder caused by a dopamine deficit in the brain. Current therapies primarily focus on dopamine modulators or replacements, such as levodopa. Although dopamine replacement can help alleviate PD symptoms, therapies targeting the underlying neurodegenerative process are limited. The study objective was to use artificial intelligence to rank the most promising repurposed drug candidates for PD. Natural language processing (NLP) techniques were used to extract text relationships from 33+ million biomedical journal articles from PubMed and map relationships between genes, proteins, drugs, diseases, etc., into a knowledge graph. Cross-domain text mining, hub network analysis, and unsupervised learning rank aggregation were performed in SemNet 2.0 to predict the most relevant drug candidates to levodopa and PD using relevance-based HeteSim scores. The top predicted adjuvant PD therapies included ebastine, an antihistamine for perennial allergic rhinitis; levocetirizine, another antihistamine; vancomycin, a powerful antibiotic; captopril, an angiotensin-converting enzyme (ACE) inhibitor; and neramexane, an N-methyl-D-aspartate (NMDA) receptor agonist. Cross-domain text mining predicted that antihistamines exhibit the capacity to synergistically alleviate Parkinsonian symptoms when used with dopamine modulators like levodopa or levodopa–carbidopa. The relationship patterns among the identified adjuvant candidates suggest that the likely therapeutic mechanism(s) of action of antihistamines for combatting the multi-factorial PD pathology include counteracting oxidative stress, amending the balance of neurotransmitters, and decreasing the proliferation of inflammatory mediators. Finally, cross-domain text mining interestingly predicted a strong relationship between PD and liver disease.
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spelling pubmed-104188612023-08-12 Literature-Based Discovery Predicts Antihistamines Are a Promising Repurposed Adjuvant Therapy for Parkinson’s Disease Tandra, Gabriella Yoone, Amy Mathew, Rhea Wang, Minzhi Hales, Chadwick M. Mitchell, Cassie S. Int J Mol Sci Article Parkinson’s disease (PD) is a movement disorder caused by a dopamine deficit in the brain. Current therapies primarily focus on dopamine modulators or replacements, such as levodopa. Although dopamine replacement can help alleviate PD symptoms, therapies targeting the underlying neurodegenerative process are limited. The study objective was to use artificial intelligence to rank the most promising repurposed drug candidates for PD. Natural language processing (NLP) techniques were used to extract text relationships from 33+ million biomedical journal articles from PubMed and map relationships between genes, proteins, drugs, diseases, etc., into a knowledge graph. Cross-domain text mining, hub network analysis, and unsupervised learning rank aggregation were performed in SemNet 2.0 to predict the most relevant drug candidates to levodopa and PD using relevance-based HeteSim scores. The top predicted adjuvant PD therapies included ebastine, an antihistamine for perennial allergic rhinitis; levocetirizine, another antihistamine; vancomycin, a powerful antibiotic; captopril, an angiotensin-converting enzyme (ACE) inhibitor; and neramexane, an N-methyl-D-aspartate (NMDA) receptor agonist. Cross-domain text mining predicted that antihistamines exhibit the capacity to synergistically alleviate Parkinsonian symptoms when used with dopamine modulators like levodopa or levodopa–carbidopa. The relationship patterns among the identified adjuvant candidates suggest that the likely therapeutic mechanism(s) of action of antihistamines for combatting the multi-factorial PD pathology include counteracting oxidative stress, amending the balance of neurotransmitters, and decreasing the proliferation of inflammatory mediators. Finally, cross-domain text mining interestingly predicted a strong relationship between PD and liver disease. MDPI 2023-08-02 /pmc/articles/PMC10418861/ /pubmed/37569714 http://dx.doi.org/10.3390/ijms241512339 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Tandra, Gabriella
Yoone, Amy
Mathew, Rhea
Wang, Minzhi
Hales, Chadwick M.
Mitchell, Cassie S.
Literature-Based Discovery Predicts Antihistamines Are a Promising Repurposed Adjuvant Therapy for Parkinson’s Disease
title Literature-Based Discovery Predicts Antihistamines Are a Promising Repurposed Adjuvant Therapy for Parkinson’s Disease
title_full Literature-Based Discovery Predicts Antihistamines Are a Promising Repurposed Adjuvant Therapy for Parkinson’s Disease
title_fullStr Literature-Based Discovery Predicts Antihistamines Are a Promising Repurposed Adjuvant Therapy for Parkinson’s Disease
title_full_unstemmed Literature-Based Discovery Predicts Antihistamines Are a Promising Repurposed Adjuvant Therapy for Parkinson’s Disease
title_short Literature-Based Discovery Predicts Antihistamines Are a Promising Repurposed Adjuvant Therapy for Parkinson’s Disease
title_sort literature-based discovery predicts antihistamines are a promising repurposed adjuvant therapy for parkinson’s disease
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10418861/
https://www.ncbi.nlm.nih.gov/pubmed/37569714
http://dx.doi.org/10.3390/ijms241512339
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