{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T04:20:29Z","timestamp":1772252429995,"version":"3.50.1"},"reference-count":77,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2024,11,2]],"date-time":"2024-11-02T00:00:00Z","timestamp":1730505600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002301","name":"Estonian Research Council","doi-asserted-by":"publisher","award":["PRG957"],"award-info":[{"award-number":["PRG957"]}],"id":[{"id":"10.13039\/501100002301","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology"],"abstract":"<jats:p>Parkinson\u2019s disease (PD) is the second-most common neurodegenerative disease worldwide. Patients are diagnosed based upon movement disorders, including bradykinesia, tremor and stiffness of movement. However, non-motor signs, including constipation, rapid eye movement sleep behavior disorder, smell deficits and pain are well recognized. Peripheral neuropathy is also increasingly recognized, as the vast majority of patients show reduced intraepidermal nerve fibers, and sensory nerve conduction and sensory function is also impaired. Many case studies in the literature show that high-dose levodopa may induce or exacerbate neuropathy in PD, which is thought to involve levodopa\u2019s metabolism to homocysteine. Here, we treated primary cultures of dorsal root ganglia and a sensory neuronal cell line with levodopa to examine effects on cell morphology, mitochondrial content and physiology, and lysosomal function. High-dose levodopa reduced mitochondrial membrane potential. At concentrations observed in the patient, levodopa enhanced immunoreactivity to beta III tubulin. Critically, levodopa reduced lysosomal content and also reduced the proportion of lysosomes that were acidic, thereby impairing their function, whereas homocysteine tended to increase lysosome content. Levodopa is a critically important drug for the treatment of PD. However, our data suggest that at concentrations observed in the patient, it has deleterious effects on sensory neurons that are not related to homocysteine.<\/jats:p>","DOI":"10.3390\/biology13110893","type":"journal-article","created":{"date-parts":[[2024,11,4]],"date-time":"2024-11-04T10:57:20Z","timestamp":1730717840000},"page":"893","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Levodopa Impairs Lysosomal Function in Sensory Neurons In Vitro"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-1696-9021","authenticated-orcid":false,"given":"Oyedele J.","family":"Olaoye","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Institute of Biomedicine and Translational Medicine, University of Tartu, 50411 Tartu, Estonia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-2224-0198","authenticated-orcid":false,"given":"Asya Esin","family":"Aksoy","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Institute of Biomedicine and Translational Medicine, University of Tartu, 50411 Tartu, Estonia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Santeri V.","family":"Hyyti\u00e4inen","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Institute of Biomedicine and Translational Medicine, University of Tartu, 50411 Tartu, Estonia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aia A.","family":"Narits","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Institute of Biomedicine and Translational Medicine, University of Tartu, 50411 Tartu, Estonia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3363-8583","authenticated-orcid":false,"given":"Miriam A.","family":"Hickey","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Institute of Biomedicine and Translational Medicine, University of Tartu, 50411 Tartu, Estonia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,11,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1016\/S1474-4422(24)00038-3","article-title":"Global, Regional, and National Burden of Disorders Affecting the Nervous System, 1990\u20132021: A Systematic Analysis for the Global Burden of Disease Study 2021","volume":"23","author":"Steinmetz","year":"2024","journal-title":"Lancet Neurol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1236","DOI":"10.1007\/BF01485901","article-title":"Verteilung Von Noradrenalin Und Dopamin (3-Hydroxytyramin) Im Gehirn Des Menschen Und Ihr Verhalten Bei Erkrankungen Des Extrapyramidalen Systems","volume":"38","author":"Ehringer","year":"1960","journal-title":"Klin. 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