{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T06:14:59Z","timestamp":1780640099781,"version":"3.54.1"},"posted":{"date-parts":[[2024,9,19]]},"group-title":"Bioinformatics","reference-count":38,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2024,9,19]],"date-time":"2024-09-19T00:00:00Z","timestamp":1726704000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2024,9,19]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>Levodopa remains the primary treatment for Parkinson\u2019s disease (PD), yet its long-term use has been associated with iron accumulation in the brain, a phenomenon linked to neurodegeneration. We utilize deep machine learning to determine plausible molecular mechanisms that may underlie the effects of levodopa on iron metabolism. Using the DRIFT platform, we performed a proteome-wide target identification of levodopa and uncovered significant interactions potentially involved in cellular iron transport. Pathway analysis revealed that levodopa may influence critical iron-related pathways, including the response of EIF2AK1 to heme deficiency, heme signaling, and ABC-family protein-mediated transport. These findings suggest that levodopa may contribute to iron dysregulation in PD by interacting with iron transporters and modulating iron-related pathways. Because levodopa is used at relatively high doses in PD, our findings provide new insight into secondary effects unrelated to being a precursor of dopamine. This highlights the need for careful consideration of its effects on iron metabolism as a consequence of use in the long-term management of PD. Further experimental validation is required to confirm these interactions, and also to explore potential strategies to mitigate iron-related side effects while preserving therapeutic efficacy.<\/jats:p>","DOI":"10.1101\/2024.09.13.612928","type":"posted-content","created":{"date-parts":[[2024,9,19]],"date-time":"2024-09-19T13:20:20Z","timestamp":1726752020000},"source":"Crossref","is-referenced-by-count":2,"title":["Comprehensive mapping of the Interaction of levodopa and iron metabolism in Parkinson\u2019s 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