{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T11:12:45Z","timestamp":1783941165620,"version":"3.55.0"},"reference-count":65,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2023,8,2]],"date-time":"2023-08-02T00:00:00Z","timestamp":1690934400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["1944247"],"award-info":[{"award-number":["1944247"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["U19-AG056169"],"award-info":[{"award-number":["U19-AG056169"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["253558"],"award-info":[{"award-number":["253558"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institute of Health","doi-asserted-by":"publisher","award":["1944247"],"award-info":[{"award-number":["1944247"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institute of Health","doi-asserted-by":"publisher","award":["U19-AG056169"],"award-info":[{"award-number":["U19-AG056169"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institute of Health","doi-asserted-by":"publisher","award":["253558"],"award-info":[{"award-number":["253558"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100014989","name":"Chan Zuckerberg Initiative","doi-asserted-by":"publisher","award":["1944247"],"award-info":[{"award-number":["1944247"]}],"id":[{"id":"10.13039\/100014989","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100014989","name":"Chan Zuckerberg Initiative","doi-asserted-by":"publisher","award":["U19-AG056169"],"award-info":[{"award-number":["U19-AG056169"]}],"id":[{"id":"10.13039\/100014989","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100014989","name":"Chan Zuckerberg Initiative","doi-asserted-by":"publisher","award":["253558"],"award-info":[{"award-number":["253558"]}],"id":[{"id":"10.13039\/100014989","id-type":"DOI","asserted-by":"publisher"}]},{"name":"McCamish Parkinson\u2019s Disease Innovation Program at Georgia Institute of Technology and Emory University","award":["1944247"],"award-info":[{"award-number":["1944247"]}]},{"name":"McCamish Parkinson\u2019s Disease Innovation Program at Georgia Institute of Technology and Emory University","award":["U19-AG056169"],"award-info":[{"award-number":["U19-AG056169"]}]},{"name":"McCamish Parkinson\u2019s Disease Innovation Program at Georgia Institute of Technology and Emory University","award":["253558"],"award-info":[{"award-number":["253558"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Parkinson\u2019s 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\u2013carbidopa. 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.<\/jats:p>","DOI":"10.3390\/ijms241512339","type":"journal-article","created":{"date-parts":[[2023,8,2]],"date-time":"2023-08-02T11:04:38Z","timestamp":1690974278000},"page":"12339","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Literature-Based Discovery Predicts Antihistamines Are a Promising Repurposed Adjuvant Therapy for Parkinson\u2019s Disease"],"prefix":"10.3390","volume":"24","author":[{"given":"Gabriella","family":"Tandra","sequence":"first","affiliation":[{"name":"Laboratory for Pathology Dynamics, Georgia Institute of Technology, Atlanta, GA 30332, USA"},{"name":"Neural Engineering Center, Georgia Institute of Technology, Atlanta, GA 30332, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy","family":"Yoone","sequence":"additional","affiliation":[{"name":"Laboratory for Pathology Dynamics, Georgia Institute of Technology, Atlanta, GA 30332, USA"},{"name":"Department of Biomedical Engineering, Georgia Institute of Technology, Emory University, Atlanta, GA 30332, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rhea","family":"Mathew","sequence":"additional","affiliation":[{"name":"Laboratory for Pathology Dynamics, Georgia Institute of Technology, Atlanta, GA 30332, USA"},{"name":"College of Computing, Georgia Institute of Technology, Atlanta, GA 30332, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minzhi","family":"Wang","sequence":"additional","affiliation":[{"name":"Laboratory for Pathology Dynamics, Georgia Institute of Technology, Atlanta, GA 30332, USA"},{"name":"Neural Engineering Center, Georgia Institute of Technology, Atlanta, GA 30332, USA"},{"name":"College of Computing, Georgia Institute of Technology, Atlanta, GA 30332, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chadwick M.","family":"Hales","sequence":"additional","affiliation":[{"name":"Department of Neurology and Center for Neurodegenerative Disease, Emory University School of Medicine, Atlanta, GA 30322, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cassie S.","family":"Mitchell","sequence":"additional","affiliation":[{"name":"Laboratory for Pathology Dynamics, Georgia Institute of Technology, Atlanta, GA 30332, USA"},{"name":"Neural Engineering Center, Georgia Institute of Technology, Atlanta, GA 30332, USA"},{"name":"Department of Biomedical Engineering, Georgia Institute of Technology, Emory University, Atlanta, GA 30332, USA"},{"name":"Machine Learning Center at Georgia Tech, Georgia Institute of Technology, Atlanta, GA 30332, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,8,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"896","DOI":"10.1016\/S0140-6736(14)61393-3","article-title":"Parkinson\u2032s disease","volume":"386","author":"Kalia","year":"2015","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"S30","DOI":"10.1016\/j.parkreldis.2017.07.033","article-title":"Neuropathology of Parkinson disease","volume":"46","author":"Dickson","year":"2018","journal-title":"Park. 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