{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T03:02:19Z","timestamp":1790996539305,"version":"4.1.0"},"reference-count":82,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,1,16]],"date-time":"2025-01-16T00:00:00Z","timestamp":1736985600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2025,1,16]],"date-time":"2025-01-16T00:00:00Z","timestamp":1736985600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["npj Biomed. Innov."],"DOI":"10.1038\/s44385-024-00005-7","type":"journal-article","created":{"date-parts":[[2025,1,16]],"date-time":"2025-01-16T10:52:26Z","timestamp":1737024746000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Exploring dopa decarboxylase as an ideal biomarker in Parkinson\u2019s disease with focus on regulatory mechanisms, cofactor influences, and metabolic implications"],"prefix":"10.1038","volume":"2","author":[{"given":"Nourhan","family":"Shebl","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed","family":"Salama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,1,16]]},"reference":[{"key":"5_CR1","first-page":"1","volume":"3","author":"W Poewe","year":"2017","unstructured":"Poewe, W. et al. Parkinson disease. Nat. Rev. Dis. Prim. 3, 1\u201321 (2017).","journal-title":"Nat. Rev. Dis. Prim."},{"key":"5_CR2","doi-asserted-by":"publisher","unstructured":"Shebl, N. et al. Metabolomic profiling reveals altered phenylalanine metabolism in Parkinson\u2019s disease in an Egyptian cohort. Front. Mol. Biosci. 11, https:\/\/doi.org\/10.3389\/fmolb.2024.1341950 (2024).","DOI":"10.3389\/fmolb.2024.1341950"},{"key":"5_CR3","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1007\/BF01994628","volume":"191","author":"P Holtz","year":"1938","unstructured":"Holtz, P., Heise, R. & L\u00fcdtke, K. Fermentativer Abbau von l-Dioxyphenylalanin (Dopa) durch Niere. Naunyn Schmiedebergs Arch. Exp. Pathol. Pharmakol. 191, 87\u2013118 (1938).","journal-title":"Naunyn Schmiedebergs Arch. Exp. Pathol. Pharmakol."},{"key":"5_CR4","doi-asserted-by":"crossref","unstructured":"Lotsios, N. S. et al. Expression of human L-dopa decarboxylase (DDC) under conditions of oxidative stress. Curr. Issues Mol. Biol. 45, 12 (2023).","DOI":"10.3390\/cimb45120635"},{"key":"5_CR5","doi-asserted-by":"publisher","DOI":"10.1186\/s40035-023-00374-w","volume":"12","author":"W Paslawski","year":"2023","unstructured":"Paslawski, W. et al. Large-scale proximity extension assay reveals CSF midkine and DOPA decarboxylase as supportive diagnostic biomarkers for Parkinson\u2019s disease. Transl. Neurodegener. 12, 42 (2023).","journal-title":"Transl. Neurodegener."},{"key":"5_CR6","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1007\/s00401-024-02706-0","volume":"147","author":"J Rutledge","year":"2024","unstructured":"Rutledge, J. et al. Comprehensive proteomics of CSF, plasma, and urine identify DDC and other biomarkers of early Parkinson\u2019s disease. Acta Neuropathol. 147, 52 (2024).","journal-title":"Acta Neuropathol."},{"key":"5_CR7","doi-asserted-by":"publisher","unstructured":"Khosousi, S. et al. Increased CSF DOPA decarboxylase correlates with lower DaT-SPECT binding: analyses in Biopark and PPMI cohorts. Mov. Disord. https:\/\/doi.org\/10.1002\/mds.29835 (2024).","DOI":"10.1002\/mds.29835"},{"key":"5_CR8","doi-asserted-by":"publisher","first-page":"1201","DOI":"10.1038\/s43587-023-00478-y","volume":"3","author":"JB Pereira","year":"2023","unstructured":"Pereira, J. B. et al. DOPA decarboxylase is an emerging biomarker for Parkinsonian disorders including preclinical Lewy body disease. Nat. Aging 3, 1201\u20131209 (2023).","journal-title":"Nat. Aging"},{"key":"5_CR9","doi-asserted-by":"publisher","first-page":"340","DOI":"10.1111\/j.1755-5949.2008.00058.x","volume":"14","author":"M Hadjiconstantinou","year":"2008","unstructured":"Hadjiconstantinou, M. & Neff, N. H. Enhancing aromatic L\u2010amino acid decarboxylase activity: implications for L\u2010DOPA treatment in Parkinson\u2019s disease. CNS Neurosci. Ther. 14, 340\u2013351 (2008).","journal-title":"CNS Neurosci. Ther."},{"key":"5_CR10","doi-asserted-by":"publisher","first-page":"6058","DOI":"10.1021\/bi00295a003","volume":"22","author":"R Maneckjee","year":"1983","unstructured":"Maneckjee, R. & Baylin, S. B. Use of radiolabeled monofluoromethyl-Dopa to define the subunit structure of human L-Dopa decarboxylase. Biochemistry 22, 6058\u20136063 (1983).","journal-title":"Biochemistry"},{"key":"5_CR11","doi-asserted-by":"publisher","first-page":"850","DOI":"10.1038\/sj.embor.embor914","volume":"4","author":"R Percudani","year":"2003","unstructured":"Percudani, R. & Peracchi, A. A genomic overview of pyridoxal\u2010phosphate\u2010dependent enzymes. EMBO Rep. 4, 850\u2013854 (2003).","journal-title":"EMBO Rep."},{"key":"5_CR12","doi-asserted-by":"crossref","unstructured":"Segura-Aguilar, J. Chapter 3\u2014Dopamine synthesis. in Clinical Studies and Therapies in Parkinson\u2019s Disease (ed. Segura-Aguilar, J.) 187\u2013193 (Academic Press, 2021).","DOI":"10.1016\/B978-0-12-822120-4.00010-1"},{"key":"5_CR13","doi-asserted-by":"publisher","first-page":"200","DOI":"10.3934\/Neuroscience.2023017","volume":"10","author":"S Ramesh","year":"2023","unstructured":"Ramesh, S. & Arachchige, A. S. P. M. Depletion of dopamine in Parkinson\u2019s disease and relevant therapeutic options: a review of the literature. AIMS Neurosci. 10, 200\u2013231 (2023).","journal-title":"AIMS Neurosci."},{"key":"5_CR14","doi-asserted-by":"publisher","first-page":"1075","DOI":"10.1007\/BF02532418","volume":"21","author":"MD Berry","year":"1996","unstructured":"Berry, M. D., Juorio, A. V., Li, X.-M. & Boulton, A. A. Aromaticl-amino acid decarboxylase: a neglected and misunderstood enzyme. Neurochem. Res. 21, 1075\u20131087 (1996).","journal-title":"Neurochem. Res."},{"key":"5_CR15","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1007\/BF02245292","volume":"108","author":"PR Buckland","year":"1992","unstructured":"Buckland, P. R., O\u2019Donovan, M. C. & McGuffin, P. Changes in dopa decarboxylase mRNA but not tyrosine hydroxylase mRNA levels in rat brain following antipsychotic treatment. Psychopharmacology 108, 98\u2013102 (1992).","journal-title":"Psychopharmacology"},{"key":"5_CR16","doi-asserted-by":"publisher","first-page":"237","DOI":"10.1016\/S0006-8993(99)01395-5","volume":"830","author":"S Cho","year":"1999","unstructured":"Cho, S., Duchemin, A. M., Neff, N. H. & Hadjiconstantinou, M. Tyrosine hydroxylase, aromatic L-amino acid decarboxylase and dopamine metabolism after chronic treatment with dopaminergic drugs. Brain Res. 830, 237\u2013245 (1999).","journal-title":"Brain Res."},{"key":"5_CR17","doi-asserted-by":"publisher","first-page":"480","DOI":"10.1124\/jpet.105.097972","volume":"317","author":"NH Neff","year":"2006","unstructured":"Neff, N. H., Wemlinger, T. A., Duchemin, A.-M. & Hadjiconstantinou, M. Clozapine modulates aromatic L-amino acid decarboxylase activity in mouse striatum. J. Pharmacol. Exp. Ther. 317, 480\u2013487 (2006).","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"5_CR18","doi-asserted-by":"publisher","first-page":"1254","DOI":"10.1097\/00004647-199711000-00014","volume":"17","author":"P Cumming","year":"1997","unstructured":"Cumming, P., Ase, A., Lalibert\u00e9, C., Kuwabara, H. & Gjedde, A. In vivo regulation of DOPA decarboxylase by dopamine receptors in rat brain. J. Cereb. Blood Flow. Metab. 17, 1254\u20131260 (1997).","journal-title":"J. Cereb. Blood Flow. Metab."},{"key":"5_CR19","doi-asserted-by":"publisher","first-page":"172","DOI":"10.1002\/syn.1071","volume":"41","author":"EH Danielsen","year":"2001","unstructured":"Danielsen, E. H., Smith, D., Hermansen, F., Gjedde, A. & Cumming, P. Acute neuroleptic stimulates DOPA decarboxylase in porcine brain in vivo. Synapse 41, 172\u2013175 (2001).","journal-title":"Synapse"},{"key":"5_CR20","doi-asserted-by":"publisher","first-page":"1332","DOI":"10.1016\/j.neuroimage.2005.11.014","volume":"30","author":"I Vernaleken","year":"2006","unstructured":"Vernaleken, I. et al. Modulation of [18F]fluorodopa (FDOPA) kinetics in the brain of healthy volunteers after acute haloperidol challenge. NeuroImage 30, 1332\u20131339 (2006).","journal-title":"NeuroImage"},{"key":"5_CR21","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1002\/syn.20119","volume":"56","author":"OT DeJesus","year":"2005","unstructured":"DeJesus, O. T. et al. Aromatic L-amino acid decarboxylase (AAAD) activity in rhesus macaque striatum after MAO-B inhibition by Ro 16-6491. Synapse 56, 54\u201356 (2005).","journal-title":"Synapse"},{"key":"5_CR22","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/S0925-4927(00)00064-0","volume":"100","author":"AM Elkashef","year":"2000","unstructured":"Elkashef, A. M. et al. 6-(18)F-DOPA PET study in patients with schizophrenia. Positron emission tomography. Psychiatry Res. 100, 1\u201311 (2000).","journal-title":"Psychiatry Res."},{"key":"5_CR23","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1016\/j.cobeha.2019.02.004","volume":"28","author":"J Turkiewicz","year":"2019","unstructured":"Turkiewicz, J., Jin Ryu, H. & Mayer, E. A. Gut microbes and behavior. Curr. Opin. Behav. Sci. 28, 72\u201377 (2019).","journal-title":"Curr. Opin. Behav. Sci."},{"key":"5_CR24","doi-asserted-by":"crossref","unstructured":"Hinson, J., Raven, P. & Chew, S. 5\u2014The adrenal glands part I: the adrenal medulla. in The Endocrine System 2nd edn (eds Hinson, J., Raven, P. & Chew, S.) 53\u201360 (Churchill Livingstone, 2010).","DOI":"10.1016\/B978-0-7020-3372-8.00005-7"},{"key":"5_CR25","doi-asserted-by":"publisher","first-page":"642","DOI":"10.3390\/ijms24010642","volume":"24","author":"MH AL Mughram","year":"2022","unstructured":"AL Mughram, M. H., Ghatge, M. S., Kellogg, G. E. & Safo, M. K. Elucidating the interaction between pyridoxine 5\u2032-phosphate oxidase and dopa decarboxylase: activation of B6-dependent enzyme. Int. J. Mol. Sci. 24, 642 (2022).","journal-title":"Int. J. Mol. Sci."},{"key":"5_CR26","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1007\/s00401-024-02739-5","volume":"147","author":"N Shebl","year":"2024","unstructured":"Shebl, N. & Salama, M. From metabolomics to proteomics: understanding the role of dopa decarboxylase in Parkinson\u2019s disease. Scientific commentary on: \u201cComprehensive proteomics of CSF, plasma, and urine identify DDC and other biomarkers of early Parkinson\u2019s disease\u201d. Acta Neuropathol. 147, 88 (2024).","journal-title":"Acta Neuropathol."},{"key":"5_CR27","doi-asserted-by":"publisher","DOI":"10.1002\/prp2.1174","volume":"12","author":"K Ikenaka","year":"2024","unstructured":"Ikenaka, K. et al. Decreased hepatic enzymes reflect the decreased vitamin B6 levels in Parkinson\u2019s disease patients. Pharmacol. Res. Perspect. 12, e1174 (2024).","journal-title":"Pharmacol. Res. Perspect."},{"key":"5_CR28","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1159\/000525234","volume":"14","author":"A Wise","year":"2022","unstructured":"Wise, A., Lemus, H. N., Fields, M., Swan, M. & Bressman, S. Refractory seizures secondary to vitamin B6 deficiency in Parkinson disease: the role of carbidopa-levodopa. Case Rep. Neurol. 14, 291\u2013295 (2022).","journal-title":"Case Rep. Neurol."},{"key":"5_CR29","doi-asserted-by":"publisher","first-page":"396","DOI":"10.1093\/clinchem\/hvab262","volume":"68","author":"A-L Bj\u00f8rke-Monsen","year":"2022","unstructured":"Bj\u00f8rke-Monsen, A.-L., Bj\u00f8rk, M.-H., Storstein, A., Ueland, P. M. & Tysnes, O.-B. Severe hyperhomocysteinemia in a patient with Parkinson disease. Clin. Chem. 68, 396\u2013401 (2022).","journal-title":"Clin. Chem."},{"key":"5_CR30","doi-asserted-by":"crossref","unstructured":"Kaleck\u00fd, K. & Bottiglieri, T. Targeted metabolomic analysis in Parkinson\u2019s disease brain frontal cortex and putamen with relation to cognitive impairment. Npj Parkinsons Dis. 9, 1 (2023).","DOI":"10.1038\/s41531-023-00531-y"},{"key":"5_CR31","doi-asserted-by":"publisher","first-page":"757","DOI":"10.1017\/S0007114510001005","volume":"104","author":"K Murakami","year":"2010","unstructured":"Murakami, K., Fukuoka Kinki Parkinson\u2019s Disease Study Group et al. Dietary intake of folate, vitamin B6, vitamin B12 and riboflavin and risk of Parkinson\u2019s disease: a case-control study in Japan. Br. J. Nutr. 104, 757\u2013764 (2010).","journal-title":"Br. J. Nutr."},{"key":"5_CR32","doi-asserted-by":"publisher","first-page":"2184","DOI":"10.1110\/ps.073022107","volume":"16","author":"FN Musayev","year":"2007","unstructured":"Musayev, F. N. et al. Crystal structure of human pyridoxal kinase: structural basis of M+ and M2+ activation. Protein Sci. 16, 2184\u20132194 (2007).","journal-title":"Protein Sci."},{"key":"5_CR33","doi-asserted-by":"publisher","first-page":"2017","DOI":"10.1212\/WNL.0b013e3181ff9685","volume":"75","author":"H Mortiboys","year":"2010","unstructured":"Mortiboys, H., Johansen, K. K., Aasly, J. O. & Bandmann, O. Mitochondrial impairment in patients with Parkinson disease with the G2019S mutation in LRRK2. Neurology 75, 2017\u20132020 (2010).","journal-title":"Neurology"},{"key":"5_CR34","doi-asserted-by":"publisher","first-page":"943","DOI":"10.3390\/nu15040943","volume":"15","author":"LK Mischley","year":"2023","unstructured":"Mischley, L. K. et al. ATP and NAD+ deficiency in Parkinson\u2019s disease. Nutrients 15, 943 (2023).","journal-title":"Nutrients"},{"key":"5_CR35","doi-asserted-by":"publisher","DOI":"10.1186\/s13024-023-00676-7","volume":"18","author":"MT Henrich","year":"2023","unstructured":"Henrich, M. T., Oertel, W. H., Surmeier, D. J. & Geibl, F. F. Mitochondrial dysfunction in Parkinson\u2019s disease\u2014a key disease hallmark with therapeutic potential. Mol. Neurodegener. 18, 83 (2023).","journal-title":"Mol. Neurodegener."},{"key":"5_CR36","doi-asserted-by":"publisher","first-page":"8924","DOI":"10.3390\/ijms21238924","volume":"21","author":"SM Bell","year":"2020","unstructured":"Bell, S. M. et al. Peripheral glycolysis in neurodegenerative diseases. Int. J. Mol. Sci. 21, 8924 (2020).","journal-title":"Int. J. Mol. Sci."},{"key":"5_CR37","doi-asserted-by":"publisher","first-page":"303","DOI":"10.1007\/s00429-010-0246-0","volume":"214","author":"P Borghammer","year":"2010","unstructured":"Borghammer, P. et al. Cortical hypometabolism and hypoperfusion in Parkinson\u2019s disease is extensive: probably even at early disease stages. Brain Struct. Funct. 214, 303\u2013317 (2010).","journal-title":"Brain Struct. Funct."},{"key":"5_CR38","doi-asserted-by":"publisher","first-page":"938","DOI":"10.1038\/npp.2012.255","volume":"38","author":"P Edison","year":"2013","unstructured":"Edison, P. et al. Microglia, amyloid, and glucose metabolism in Parkinson\u2019s disease with and without dementia. Neuropsychopharmacology 38, 938\u2013949 (2013).","journal-title":"Neuropsychopharmacology"},{"key":"5_CR39","doi-asserted-by":"publisher","first-page":"1111","DOI":"10.1016\/j.neurobiolaging.2013.11.001","volume":"35","author":"L Dunn","year":"2014","unstructured":"Dunn, L. et al. Dysregulation of glucose metabolism is an early event in sporadic Parkinson\u2019s disease. Neurobiol. Aging 35, 1111\u20131115 (2014).","journal-title":"Neurobiol. Aging"},{"key":"5_CR40","unstructured":"National Center for Biotechnology Information. PubChem Pathway Summary for Pathway SMP0000006, Tyrosine Metabolism. PathBank, https:\/\/pubchem.ncbi.nlm.nih.gov\/pathway\/PathBank:SMP0000006 (2024)."},{"key":"5_CR41","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1530\/EC-17-0059","volume":"6","author":"FL Martins Pe\u00e7anha","year":"2017","unstructured":"Martins Pe\u00e7anha, F. L., dos Santos, R. S. & da-Silva, W. S. Thyroid states regulate subcellular glucose phosphorylation activity in male mice. Endocr. Connect. 6, 311\u2013322 (2017).","journal-title":"Endocr. Connect."},{"key":"5_CR42","first-page":"e14858","volume":"9","author":"DA Mendez","year":"2021","unstructured":"Mendez, D. A. & Ortiz, R. M. Thyroid hormones and the potential for regulating glucose metabolism in cardiomyocytes during insulin resistance and T2DM. PhysiolRep. 9, e14858 (2021).","journal-title":"PhysiolRep."},{"key":"5_CR43","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1089\/thy.2007.0250","volume":"18","author":"M-E Harper","year":"2008","unstructured":"Harper, M.-E. & Seifert, E. L. Thyroid hormone effects on mitochondrial energetics. Thyroid\u00ae 18, 145\u2013156 (2008).","journal-title":"Thyroid\u00ae"},{"key":"5_CR44","doi-asserted-by":"publisher","first-page":"369","DOI":"10.1002\/stem.3129","volume":"38","author":"L Noli","year":"2020","unstructured":"Noli, L. et al. Effects of thyroid hormone on mitochondria and metabolism of human preimplantation embryos. Stem Cells 38, 369 (2020).","journal-title":"Stem Cells"},{"key":"5_CR45","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1677\/jme.0.0260067","volume":"26","author":"C Wrutniak-Cabello","year":"2001","unstructured":"Wrutniak-Cabello, C., Casas, F. & Cabello, G. Thyroid hormone action in mitochondria. J. Mol. Endocrinol. 26, 67\u201377 (2001).","journal-title":"J. Mol. Endocrinol."},{"key":"5_CR46","doi-asserted-by":"publisher","first-page":"361","DOI":"10.1210\/js.2017-00434","volume":"2","author":"IS Al-Gadi","year":"2018","unstructured":"Al-Gadi, I. S., Haas, R. H., Falk, M. J., Goldstein, A. & McCormack, S. E. Endocrine disorders in primary mitochondrial disease. J. Endocr. Soc. 2, 361\u2013373 (2018).","journal-title":"J. Endocr. Soc."},{"key":"5_CR47","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1530\/JOE-12-0304","volume":"217","author":"S Maity","year":"2013","unstructured":"Maity, S., Kar, D., De, K., Chander, V. & Bandyopadhyay, A. Hyperthyroidism causes cardiac dysfunction by mitochondrial impairment and energy depletion. J. Endocrinol. 217, 215\u2013228 (2013).","journal-title":"J. Endocrinol."},{"key":"5_CR48","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1007\/BF03346767","volume":"1","author":"F Massara","year":"1978","unstructured":"Massara, F., Camanni, F., Vergano, V., Belforte, L. & Molinatti, G. M. Inhibition of thyrotropin and prolactin secretion by dopamine in man. J. Endocrinol. Invest. 1, 25\u201330 (1978).","journal-title":"J. Endocrinol. Invest."},{"key":"5_CR49","doi-asserted-by":"publisher","first-page":"387","DOI":"10.1210\/jcem-51-2-387","volume":"51","author":"EM Kaptein","year":"1980","unstructured":"Kaptein, E. M., Spencer, C. A., Kamiel, M. B. & Nicoloff, J. T. Prolonged dopamine administration and thyroid hormone economy in normal and critically ill subjects. J. Clin. Endocrinol. Metab. 51, 387\u2013393 (1980).","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"5_CR50","doi-asserted-by":"publisher","first-page":"548","DOI":"10.1590\/S1807-59322010000500013","volume":"65","author":"JC Pereira","year":"2010","unstructured":"Pereira, J. C., Pradella-Hallinan, M. & de Lins Pessoa, H. Imbalance between thyroid hormones and the dopaminergic system might be central to the pathophysiology of restless legs syndrome: a hypothesis. Clinics 65, 548\u2013554 (2010).","journal-title":"Clinics"},{"key":"5_CR51","doi-asserted-by":"publisher","first-page":"341","DOI":"10.3181\/00379727-187-42674","volume":"187","author":"DJ Haisenleder","year":"1988","unstructured":"Haisenleder, D. J., Moy, J. A., Gala, R. R. & Lawson, D. M. The effect of dopamine antagonists and\/or VIP on TRH- or VIP-induced prolactin release in estrogen- and progesterone-treated ovariectomized rats. Proc. Soc. Exp. Biol. Med. 187, 341\u2013349 (1988).","journal-title":"Proc. Soc. Exp. Biol. Med."},{"key":"5_CR52","doi-asserted-by":"crossref","unstructured":"Montanelli, L. et al. Drugs and other substances interfering with thyroid function. in Thyroid Diseases: Pathogenesis, Diagnosis and Treatment (eds Vitti, P. & Hegedus, L.) 1\u201329 (Springer International Publishing, 2018).","DOI":"10.1007\/978-3-319-29195-6_27-1"},{"key":"5_CR53","unstructured":"Shahid, M. A., Ashraf, M. A. & Sharma, S. Physiology, Thyroid Hormone. In StatPearls (StatPearls Publishing LLC.: Treasure Island, FL, USA, 2022)."},{"key":"5_CR54","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1210\/er.2013-1087","volume":"35","author":"C Fekete","year":"2014","unstructured":"Fekete, C. & Lechan, R. M. Central regulation of hypothalamic-pituitary-thyroid axis under physiological and pathophysiological conditions. Endocr. Rev. 35, 159\u2013194 (2014).","journal-title":"Endocr. Rev."},{"key":"5_CR55","doi-asserted-by":"publisher","first-page":"360","DOI":"10.1002\/mdc3.13656","volume":"10","author":"SA Schneider","year":"2023","unstructured":"Schneider, S. A., Tschaidse, L. & Reisch, N. Thyroid disorders and movement disorders\u2014a systematic review. Mov. Disord. Clin. Pract. 10, 360\u2013368 (2023).","journal-title":"Mov. Disord. Clin. Pract."},{"key":"5_CR56","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1136\/bmj.293.6538.38","volume":"293","author":"TH Caradoc-Davies","year":"1986","unstructured":"Caradoc-Davies, T. H. Resolution of dyskinesia and the \u201con-off\u201d phenomenon in thyrotoxic patients with Parkinson\u2019s disease after antithyroid treatment. Br. Med. J. 293, 38\u201339 (1986).","journal-title":"Br. Med. J."},{"key":"5_CR57","volume":"2014","author":"M Min\u00e1r","year":"2014","unstructured":"Min\u00e1r, M. & Valkovi\u010d, P. Thyroid-induced worsening of parkinsonian tremor resistant to drugs and subthalamic nucleus deep brain stimulation. Case Rep. Neurol. Med. 2014, 489275 (2014).","journal-title":"Case Rep. Neurol. Med."},{"key":"5_CR58","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1016\/S0167-4943(01)00196-0","volume":"33","author":"H Tandeter","year":"2001","unstructured":"Tandeter, H., Levy, A., Gutman, G. & Shvartzman, P. Subclinical thyroid disease in patients with Parkinson\u2019s disease. Arch. Gerontol. Geriatr. 33, 295\u2013300 (2001).","journal-title":"Arch. Gerontol. Geriatr."},{"key":"5_CR59","doi-asserted-by":"publisher","unstructured":"Tan, Y. et al. Thyroid hormone levels and structural parameters of thyroid homeostasis are correlated with motor subtype and disease severity in euthyroid patients with Parkinson\u2019s disease. Int. J. Neurosci. https:\/\/doi.org\/10.1080\/00207454.2020.1744595 (2021).","DOI":"10.1080\/00207454.2020.1744595"},{"key":"5_CR60","doi-asserted-by":"publisher","first-page":"1058","DOI":"10.1002\/mds.10475","volume":"18","author":"JM Garc\u00eda-Moreno","year":"2003","unstructured":"Garc\u00eda-Moreno, J. M. & Chac\u00f3n-Pe\u00f1a, J. Hypothyroidism and Parkinson\u2019s disease and the issue of diagnostic confusion. Mov. Disord. 18, 1058\u20131059 (2003).","journal-title":"Mov. Disord."},{"key":"5_CR61","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1080\/00325481.1993.11945738","volume":"94","author":"HB Tandeter","year":"1993","unstructured":"Tandeter, H. B. & Shvartzman, P. Parkinson\u2019s disease camouflaging early signs of hypothyroidism. Postgrad. Med. 94, 187\u2013190 (1993).","journal-title":"Postgrad. Med."},{"key":"5_CR62","doi-asserted-by":"publisher","first-page":"3864","DOI":"10.1210\/jcem.86.8.7749","volume":"86","author":"EL Constant","year":"2001","unstructured":"Constant, E. L. et al. Cerebral blood flow and glucose metabolism in hypothyroidism: a positron emission tomography study. J. Clin. Endocrinol. Metab. 86, 3864\u20133870 (2001).","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"5_CR63","doi-asserted-by":"publisher","first-page":"552","DOI":"10.1136\/bmj.2.5656.552","volume":"2","author":"J Braham","year":"1969","unstructured":"Braham, J. et al. Oral phenylalanine and tyrosine tolerance tests in Parkinsonian patients. BMJ 2, 552\u2013555 (1969).","journal-title":"BMJ"},{"key":"5_CR64","doi-asserted-by":"publisher","first-page":"423","DOI":"10.3233\/JPD-150736","volume":"6","author":"M Hirayama","year":"2016","unstructured":"Hirayama, M., Tsunoda, M., Yamamoto, M., Tsuda, T. & Ohno, K. Serum tyrosine-to-phenylalanine ratio is low in Parkinson\u2019s disease. J. Parkinsons Dis. 6, 423\u2013431 (2016).","journal-title":"J. Parkinsons Dis."},{"key":"5_CR65","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1016\/j.mehy.2018.06.018","volume":"118","author":"GB Steventon","year":"2018","unstructured":"Steventon, G. B. & Mitchell, S. C. Phenylalanine hydroxylase: a biomarker of disease susceptibility in Parkinson\u2019s disease and Amyotrophic lateral sclerosis. Med. Hypotheses 118, 29\u201333 (2018).","journal-title":"Med. Hypotheses"},{"key":"5_CR66","doi-asserted-by":"publisher","unstructured":"Rawlings, L., Turton, L., Mitchell, S. C., & Steventon, G. B. Drug S-oxidation and phenylalaninehydroxylase: A biomarker for neurodegenerative susceptibility in Parkinson\u2019s disease and amyotrophic lateralsclerosis. Drug Metab. Pers. Ther. 34, https:\/\/doi.org\/10.1515\/dmpt-2018-0038 (2019).","DOI":"10.1515\/dmpt-2018-0038"},{"key":"5_CR67","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1016\/j.ncl.2019.12.002","volume":"38","author":"W Poewe","year":"2020","unstructured":"Poewe, W. & Mahlknecht, P. Pharmacologic treatment of motor symptoms associated with Parkinson disease. Neurol. Clin. 38, 255\u2013267 (2020).","journal-title":"Neurol. Clin."},{"key":"5_CR68","doi-asserted-by":"publisher","first-page":"1842","DOI":"10.3390\/ijms24031842","volume":"24","author":"EA Katunina","year":"2023","unstructured":"Katunina, E. A. et al. Searching for biomarkers in the blood of patients at risk of developing Parkinson\u2019s disease at the prodromal stage. Int. J. Mol. Sci. 24, 1842 (2023).","journal-title":"Int. J. Mol. Sci."},{"key":"5_CR69","doi-asserted-by":"publisher","first-page":"108","DOI":"10.1016\/j.parkreldis.2018.02.023","volume":"50","author":"DS Goldstein","year":"2018","unstructured":"Goldstein, D. S., Holmes, C., Lopez, G. J., Wu, T. & Sharabi, Y. Cerebrospinal fluid biomarkers of central dopamine deficiency predict Parkinson\u2019s disease. Parkinsonism Relat. Disord. 50, 108\u2013112 (2018).","journal-title":"Parkinsonism Relat. Disord."},{"key":"5_CR70","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41531-021-00199-2","volume":"7","author":"F Depierreux","year":"2021","unstructured":"Depierreux, F. et al. Parkinson\u2019s disease multimodal imaging: F-DOPA PET, neuromelanin-sensitive and quantitative iron-sensitive MRI. Npj Parkinsons Dis. 7, 1\u201310 (2021).","journal-title":"Npj Parkinsons Dis."},{"key":"5_CR71","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1016\/j.nbd.2012.05.018","volume":"48","author":"J Blesa","year":"2012","unstructured":"Blesa, J. et al. The nigrostriatal system in the presymptomatic and symptomatic stages in the MPTP monkey model: a PET, histological and biochemical study. Neurobiol. Dis. 48, 79\u201391 (2012).","journal-title":"Neurobiol. Dis."},{"key":"5_CR72","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1034\/j.1600-079X.2001.300404.x","volume":"30","author":"M Ghaemi","year":"2001","unstructured":"Ghaemi, M., Rudolf, J., Hilker, R., Herholz, K. & Heiss, W. D. Increased pineal Fdopa uptake is related to severity of Parkinson\u2019s disease\u2013A PET study. J. Pineal Res. 30, 213\u2013219 (2001).","journal-title":"J. Pineal Res."},{"key":"5_CR73","doi-asserted-by":"publisher","first-page":"381","DOI":"10.1016\/j.nbd.2007.09.004","volume":"29","author":"RY Moore","year":"2008","unstructured":"Moore, R. Y., Whone, A. L. & Brooks, D. J. Extrastriatal monoamine neuron function in Parkinson\u2019s disease: an 18F-dopa PET study. Neurobiol. Dis. 29, 381\u2013390 (2008).","journal-title":"Neurobiol. Dis."},{"key":"5_CR74","doi-asserted-by":"publisher","first-page":"1125","DOI":"10.1093\/brain\/124.6.1125","volume":"124","author":"V Kaasinen","year":"2001","unstructured":"Kaasinen, V. et al. Increased frontal [(18)F]fluorodopa uptake in early Parkinson\u2019s disease: sex differences in the prefrontal cortex. Brain 124, 1125\u20131130 (2001).","journal-title":"Brain"},{"key":"5_CR75","unstructured":"Arendt, J. & Aulinas, A. Physiology of the pineal gland and melatonin. in Endotext (eds Feingold, K. R. et al.) (MDText.com, Inc., 2000)."},{"key":"5_CR76","unstructured":"Walker, E. P. & Tadi, P. Neuroanatomy, Nucleus Raphe. 2023 May 1. In StatPearls [Internet] (Treasure Island (FL): StatPearls Publishing, 2025)."},{"key":"5_CR77","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1016\/bs.irn.2019.06.013","volume":"146","author":"S Vegas-Suarez","year":"2019","unstructured":"Vegas-Suarez, S. et al. Dysfunction of serotonergic neurons in Parkinson\u2019s disease and dyskinesia. Int. Rev. Neurobiol. 146, 259\u2013279 (2019).","journal-title":"Int. Rev. Neurobiol."},{"key":"5_CR78","doi-asserted-by":"publisher","DOI":"10.1155\/2016\/3472032","volume":"2016","author":"JM Mack","year":"2016","unstructured":"Mack, J. M. et al. Melatoninergic system in Parkinson\u2019s disease: from neuroprotection to the management of motor and nonmotor symptoms. Oxid. Med. Cell. Longev. 2016, 3472032 (2016).","journal-title":"Oxid. Med. Cell. Longev."},{"key":"5_CR79","doi-asserted-by":"publisher","DOI":"10.1186\/s40035-024-00421-0","volume":"13","author":"E Appleton","year":"2024","unstructured":"Appleton, E. et al. DOPA-decarboxylase is elevated in CSF, but not plasma, in prodromal and de novo Parkinson\u2019s disease. Transl. Neurodegener. 13, 31 (2024).","journal-title":"Transl. Neurodegener."},{"key":"5_CR80","doi-asserted-by":"publisher","first-page":"489","DOI":"10.1212\/WNL.26.5.489","volume":"26","author":"JP Lakke","year":"1976","unstructured":"Lakke, J. P. & Teelken, A. W. Amino acid abnormalities in cerebrospinal fluid of patients with parkinsonism and extrapyramidal disorders. Neurol. 26, 489\u2013493 (1976).","journal-title":"Neurol."},{"key":"5_CR81","doi-asserted-by":"publisher","first-page":"1097","DOI":"10.1007\/s00426-017-0957-4","volume":"83","author":"S K\u00fchn","year":"2017","unstructured":"K\u00fchn, S. et al. Food for thought: association between dietary tyrosine and cognitive performance in younger and older adults. Psychol. Res. 83, 1097 (2017).","journal-title":"Psychol. Res."},{"key":"5_CR82","doi-asserted-by":"publisher","DOI":"10.1186\/s40035-024-00430-z","volume":"13","author":"K Lau","year":"2024","unstructured":"Lau, K., Kotzur, R. & Richter, F. Blood\u2013brain barrier alterations and their impact on Parkinson\u2019s disease pathogenesis and therapy. Transl. Neurodegener. 13, 37 (2024).","journal-title":"Transl. Neurodegener."}],"container-title":["npj Biomedical Innovations"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s44385-024-00005-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s44385-024-00005-7","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s44385-024-00005-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,16]],"date-time":"2025-01-16T11:41:37Z","timestamp":1737027697000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s44385-024-00005-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,16]]},"references-count":82,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["5"],"URL":"https:\/\/doi.org\/10.1038\/s44385-024-00005-7","relation":{},"ISSN":["3005-1444"],"issn-type":[{"value":"3005-1444","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,16]]},"assertion":[{"value":"1 August 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 December 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 January 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"2"}}