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Quadracci Professor in Parkinson\u2019s Research Endowment"},{"DOI":"10.13039\/501100004794","name":"Centre National de la Recherche Scientifique","doi-asserted-by":"publisher","award":["International Research Project SuperO2"],"award-info":[{"award-number":["International Research Project SuperO2"]}],"id":[{"id":"10.13039\/501100004794","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Advancing a Healthier Wisconsin Endowment, G. Frederick Kasten, Jr Endowed Professorship in Parkinson\u2019s Disease Research"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Commun Biol"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Parkinson\u2019s disease is managed using levodopa; however, as Parkinson\u2019s disease progresses, patients require increased doses of levodopa, which can cause undesirable side effects. Additionally, the oral bioavailability of levodopa decreases in Parkinson\u2019s disease patients due to the increased metabolism of levodopa to dopamine by gut bacteria, <jats:italic>Enterococcus faecalis<\/jats:italic>, resulting in decreased neuronal uptake and dopamine formation. Parkinson\u2019s disease patients have varying levels of these bacteria. Thus, decreasing bacterial metabolism is a promising therapeutic approach to enhance the bioavailability of levodopa in the brain. In this work, we show that Mito-<jats:italic>ortho<\/jats:italic>-HNK, formed by modification of a naturally occurring molecule, honokiol, conjugated to a triphenylphosphonium moiety, mitigates the metabolism of levodopa\u2014alone or combined with carbidopa\u2014to dopamine. Mito-<jats:italic>ortho<\/jats:italic>-HNK suppresses the growth of <jats:italic>E. faecalis<\/jats:italic>, decreases dopamine levels in the gut, and increases dopamine levels in the brain. Mitigating the gut bacterial metabolism of levodopa as shown here could enhance its efficacy.<\/jats:p>","DOI":"10.1038\/s42003-024-06330-2","type":"journal-article","created":{"date-parts":[[2024,5,30]],"date-time":"2024-05-30T16:02:03Z","timestamp":1717084923000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Mitigating gut microbial degradation of levodopa and enhancing brain dopamine: Implications in Parkinson\u2019s disease"],"prefix":"10.1038","volume":"7","author":[{"given":"Gang","family":"Cheng","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2976-7785","authenticated-orcid":false,"given":"Micael","family":"Hardy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9678-748X","authenticated-orcid":false,"given":"Cecilia J.","family":"Hillard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jimmy B.","family":"Feix","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9180-8296","authenticated-orcid":false,"given":"Balaraman","family":"Kalyanaraman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,5,30]]},"reference":[{"key":"6330_CR1","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1159\/000215875","volume":"62","author":"RA Hauser","year":"2009","unstructured":"Hauser, R. 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