{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T15:33:54Z","timestamp":1786980834388,"version":"build-2736575974"},"reference-count":48,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,12,15]],"date-time":"2025-12-15T00:00:00Z","timestamp":1765756800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T00:00:00Z","timestamp":1768348800000},"content-version":"vor","delay-in-days":30,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100012990","name":"Universit\u00e0 degli Studi di Siena","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100012990","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Cell Mol Neurobiol"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Lesch\u2013Nyhan disease (LND) is an ultra-rare X-linked inborn error of metabolism caused by complete or partial deficiency of hypoxanthine-guanine phosphoribosyltransferase (HPRT), a key enzyme in the purine salvage pathway. This defect leads to uric acid overproduction and a broad spectrum of neurological and behavioral manifestations, whose severity depends on the degree of residual enzymatic activity. Although emerging evidence implicates HPRT deficiency in widespread cellular dysfunctions, particularly within midbrain dopaminergic neurons, the molecular mechanisms underlying the neurobehavioral phenotype of HPRT deficiency remain poorly understood and are not adequately explained by purine metabolism dysfunctions alone. Although proteomics represents a powerful approach for elucidating molecular alterations underlying disease, it has so far found only limited application in LND research. To address this gap, we provide here the first proteomic study combined with clinical biochemistry data and pro-inflammatory cytokines profiling of plasma samples from 29 HPRT deficient individuals (21 with classic LND and 8 with Lesch\u2013Nyhan variants \u2013 LNV). We suggest that plasma proteomics might be a potential tool in LND for monitoring disease progression and therapeutic response, potentially paving the way for targeted treatment strategies that extend beyond the purine salvage pathway to address the currently unmet clinical needs of LND patients.<\/jats:p>\n                  <jats:p>\n                    <jats:bold>Graphical Abstract<\/jats:bold>\n                  <\/jats:p>","DOI":"10.1007\/s10571-025-01644-z","type":"journal-article","created":{"date-parts":[[2025,12,15]],"date-time":"2025-12-15T17:06:40Z","timestamp":1765818400000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Uncovering Proteomic and Biochemical Alterations in Plasma from Lesch\u2013Nyhan Disease Patients"],"prefix":"10.1007","volume":"46","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-9551-2731","authenticated-orcid":false,"given":"Sundas","family":"Javed","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9657-4169","authenticated-orcid":false,"given":"Daniela","family":"Braconi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-1392-9454","authenticated-orcid":false,"given":"Haidara","family":"Nadwa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-7035-4022","authenticated-orcid":false,"given":"Alessandro","family":"Paffetti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0896-7692","authenticated-orcid":false,"given":"Gabriella","family":"Jacomelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9021-6451","authenticated-orcid":false,"given":"Vanna","family":"Micheli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4622-7054","authenticated-orcid":false,"given":"Barbara","family":"Marzocchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6976-9086","authenticated-orcid":false,"given":"Annalisa","family":"Santucci","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0016-0728","authenticated-orcid":false,"given":"Giulia","family":"Bernardini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,12,15]]},"reference":[{"issue":"7620","key":"1644_CR1","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1038\/nature19949","volume":"537","author":"R Aebersold","year":"2016","unstructured":"Aebersold R, Mann M (2016) Mass-spectrometric exploration of proteome structure and function. Nature 537(7620):347\u2013355. https:\/\/doi.org\/10.1038\/nature19949","journal-title":"Nature"},{"key":"1644_CR2","doi-asserted-by":"publisher","first-page":"2790","DOI":"10.1007\/s12035-016-9866-6","volume":"54","author":"H Biasibetti","year":"2017","unstructured":"Biasibetti H, Pierozan P, Rodrigues AF et al (2017) Hypoxanthine intrastriatal administration alters neuroinflammatory profile and redox status in striatum of infant and young adult rats. Mol Neurobiol 54:2790\u20132800. https:\/\/doi.org\/10.1007\/s12035-016-9866-6","journal-title":"Mol Neurobiol"},{"key":"1644_CR3","doi-asserted-by":"publisher","first-page":"4098","DOI":"10.1007\/s12035-017-0634-z","volume":"55","author":"H Biasibetti-Brendler","year":"2018","unstructured":"Biasibetti-Brendler H, Schmitz F, Pierozan P et al (2018) Hypoxanthine induces neuroenergetic impairment and cell death in striatum of young adult Wistar rats. Mol Neurobiol 55:4098\u20134106. https:\/\/doi.org\/10.1007\/s12035-017-0634-z","journal-title":"Mol Neurobiol"},{"key":"1644_CR4","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1016\/j.tins.2014.12.006","volume":"38","author":"A Borsini","year":"2015","unstructured":"Borsini A, Zunszain PA, Thuret S, Pariante CM (2015) The role of inflammatory cytokines as key modulators of neurogenesis. Trends Neurosci 38:145\u2013157. https:\/\/doi.org\/10.1016\/j.tins.2014.12.006","journal-title":"Trends Neurosci"},{"key":"1644_CR5","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2016.08.016","author":"D Braconi","year":"2016","unstructured":"Braconi D, Bernardini G, Paffetti A et al (2016) Comparative proteomics in alkaptonuria provides insights into inflammation and oxidative stress. Int J Biochem Cell Biol. https:\/\/doi.org\/10.1016\/j.biocel.2016.08.016","journal-title":"Int J Biochem Cell Biol"},{"key":"1644_CR6","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1080\/14789450.2021.1918549","volume":"18","author":"D Braconi","year":"2021","unstructured":"Braconi D, Bernardini G, Spiga O, Santucci A (2021) Leveraging proteomics in orphan disease research: pitfalls and potential. Expert Rev Proteom 18:315\u2013327. https:\/\/doi.org\/10.1080\/14789450.2021.1918549","journal-title":"Expert Rev Proteom"},{"key":"1644_CR7","doi-asserted-by":"publisher","first-page":"3668","DOI":"10.3390\/CELLS11223668","volume":"11","author":"D Braconi","year":"2022","unstructured":"Braconi D, Geminiani M, Psarelli EE et al (2022) Effects of nitisinone on oxidative and inflammatory markers in alkaptonuria: results from SONIA1 and SONIA2 studies. Cells 11:3668. https:\/\/doi.org\/10.3390\/CELLS11223668","journal-title":"Cells"},{"key":"1644_CR8","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1080\/14789450.2025.2468300","volume":"22","author":"D Braconi","year":"2025","unstructured":"Braconi D, Nadwa H, Bernardini G, Santucci A (2025) Omics and rare diseases: challenges, applications, and future perspectives. Expert Rev Proteom 22:107\u2013122. https:\/\/doi.org\/10.1080\/14789450.2025.2468300","journal-title":"Expert Rev Proteom"},{"key":"1644_CR9","doi-asserted-by":"publisher","DOI":"10.1016\/J.NEULET.2020.135540","volume":"741","author":"Y Cai","year":"2021","unstructured":"Cai Y, Xing L, Yang T et al (2021) The neurodevelopmental role of dopaminergic signaling in neurological disorders. Neurosci Lett 741:135540. https:\/\/doi.org\/10.1016\/J.NEULET.2020.135540","journal-title":"Neurosci Lett"},{"key":"1644_CR10","doi-asserted-by":"publisher","DOI":"10.3390\/metabo13070787","author":"M Camici","year":"2023","unstructured":"Camici M, Garcia-Gil M, Allegrini S et al (2023) Inborn errors of purine salvage and catabolism. Metabolites. https:\/\/doi.org\/10.3390\/metabo13070787","journal-title":"Metabolites"},{"key":"1644_CR11","doi-asserted-by":"publisher","first-page":"2317","DOI":"10.1093\/hmg\/ddp164","volume":"18","author":"I Ceballos-Picot","year":"2009","unstructured":"Ceballos-Picot I, Mockel L, Potier M-C et al (2009) Hypoxanthine-guanine phosphoribosyl transferase regulates early developmental programming of dopamine neurons: implications for Lesch\u2013Nyhan disease pathogenesis. Hum Mol Genet 18:2317\u201327. https:\/\/doi.org\/10.1093\/hmg\/ddp164","journal-title":"Hum Mol Genet"},{"key":"1644_CR12","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1186\/s13023-014-0219-0","volume":"10","author":"I Ceballos-Picot","year":"2015","unstructured":"Ceballos-Picot I, Le Dantec A, Brassier A et al (2015) New biomarkers for early diagnosis of Lesch\u2013Nyhan disease revealed by metabolic analysis on a large cohort of patients. Orphanet J Rare Dis 10:7. https:\/\/doi.org\/10.1186\/s13023-014-0219-0","journal-title":"Orphanet J Rare Dis"},{"key":"1644_CR13","doi-asserted-by":"publisher","first-page":"110133","DOI":"10.1016\/J.NEUROPHARM.2024.110133","volume":"260","author":"H Chen","year":"2024","unstructured":"Chen H, Li J, Huang Z et al (2024) Dopaminergic system and neurons: role in multiple neurological diseases. Neuropharmacology 260:110133. https:\/\/doi.org\/10.1016\/J.NEUROPHARM.2024.110133","journal-title":"Neuropharmacology"},{"issue":"4","key":"1644_CR14","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1111\/J.1469-8749.1982.TB13621.X","volume":"24","author":"R Christie","year":"1982","unstructured":"Christie R, Bay C, Kaufman IA et al (1982) Lesch\u2013Nyhan Disease: clinical experience with nineteen patients. Dev Med Child Neurol 24(4):293\u2013306. https:\/\/doi.org\/10.1111\/J.1469-8749.1982.TB13621.X","journal-title":"Dev Med Child Neurol"},{"key":"1644_CR15","doi-asserted-by":"publisher","first-page":"216","DOI":"10.1002\/AJMG.B.30593","volume":"147","author":"P Costa-Mallen","year":"2008","unstructured":"Costa-Mallen P, Checkoway H, Zabeti A et al (2008) The functional polymorphism of the hemoglobin-binding protein haptoglobin influences susceptibility to idiopathic Parkinson\u2019s disease. Am J Med Genet B Neuropsychiatr Genet 147:216\u2013222. https:\/\/doi.org\/10.1002\/AJMG.B.30593","journal-title":"Am J Med Genet B Neuropsychiatr Genet"},{"key":"1644_CR16","doi-asserted-by":"publisher","first-page":"1939","DOI":"10.1093\/hmg\/ddq072","volume":"19","author":"S Cristini","year":"2010","unstructured":"Cristini S, Navone S, Canzi L et al (2010) Human neural stem cells: a model system for the study of Lesch\u2013Nyhan disease neurological aspects. Hum Mol Genet 19:1939\u20131950. https:\/\/doi.org\/10.1093\/hmg\/ddq072","journal-title":"Hum Mol Genet"},{"key":"1644_CR17","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3389\/fncel.2016.00018","volume":"10","author":"K Davalieva","year":"2016","unstructured":"Davalieva K, Kostovska IM, Dwork AJ (2016) Proteomics research in schizophrenia. Front Cell Neurosci 10:1\u201322. https:\/\/doi.org\/10.3389\/fncel.2016.00018","journal-title":"Front Cell Neurosci"},{"key":"1644_CR18","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1080\/01677063.2022.2129632","volume":"36","author":"AR Dinasarapu","year":"2022","unstructured":"Dinasarapu AR, Sutcliffe DJ, Seifar F et al (2022) Abnormalities of neural stem cells in Lesch\u2013Nyhan disease. J Neurogenet 36:81\u201387. https:\/\/doi.org\/10.1080\/01677063.2022.2129632","journal-title":"J Neurogenet"},{"key":"1644_CR19","doi-asserted-by":"publisher","first-page":"901","DOI":"10.1007\/s10571-019-00700-9","volume":"39","author":"A Dixit","year":"2019","unstructured":"Dixit A, Mehta R, Singh AK (2019) Proteomics in human Parkinson\u2019s disease: present scenario and future directions. Cell Mol Neurobiol 39:901\u2013915. https:\/\/doi.org\/10.1007\/s10571-019-00700-9","journal-title":"Cell Mol Neurobiol"},{"key":"1644_CR20","doi-asserted-by":"publisher","first-page":"280","DOI":"10.1016\/j.ymgme.2014.05.012","volume":"112","author":"R Fu","year":"2014","unstructured":"Fu R, Chen C-J, Jinnah HA (2014) Genotypic and phenotypic spectrum in attenuated variants of Lesch\u2013Nyhan disease. Mol Genet Metab 112:280\u20135. https:\/\/doi.org\/10.1016\/j.ymgme.2014.05.012","journal-title":"Mol Genet Metab"},{"key":"1644_CR21","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1016\/j.ymgme.2014.11.001","volume":"114","author":"R Fu","year":"2015","unstructured":"Fu R, Sutcliffe D, Zhao H et al (2015) Clinical severity in Lesch\u2013Nyhan disease: the role of residual enzyme and compensatory pathways. Mol Genet Metab 114:55\u201361. https:\/\/doi.org\/10.1016\/j.ymgme.2014.11.001","journal-title":"Mol Genet Metab"},{"key":"1644_CR22","doi-asserted-by":"publisher","first-page":"3404","DOI":"10.1002\/EJI.200939291","volume":"39","author":"G Galicia","year":"2009","unstructured":"Galicia G, Maes W, Verbinnen B et al (2009) Haptoglobin deficiency facilitates the development of autoimmune inflammation. Eur J Immunol 39:3404\u20133412. https:\/\/doi.org\/10.1002\/EJI.200939291;WGROUP:STRING:PUBLICATION","journal-title":"Eur J Immunol"},{"key":"1644_CR23","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1002\/ana.24191","volume":"76","author":"M G\u00f6ttle","year":"2014","unstructured":"G\u00f6ttle M, Prudente CN, Fu R et al (2014) Loss of dopamine phenotype among midbrain neurons in Lesch\u2013Nyhan disease. Ann Neurol 76:95\u2013107. https:\/\/doi.org\/10.1002\/ana.24191","journal-title":"Ann Neurol"},{"key":"1644_CR24","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1038\/mt.2009.178","volume":"18","author":"G-H Guibinga","year":"2010","unstructured":"Guibinga G-H, Hsu S, Friedmann T (2010) Deficiency of the housekeeping gene hypoxanthine-guanine phosphoribosyltransferase (HPRT) dysregulates neurogenesis. Mol Ther 18:54\u201362. https:\/\/doi.org\/10.1038\/mt.2009.178","journal-title":"Mol Ther"},{"key":"1644_CR25","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms7555","author":"A Ives","year":"2015","unstructured":"Ives A, Nomura J, Martinon F et al (2015) Xanthine oxidoreductase regulates macrophage IL1\u03b2 secretion upon NLRP3 inflammasome activation. Nat Commun. https:\/\/doi.org\/10.1038\/ncomms7555","journal-title":"Nat Commun"},{"key":"1644_CR26","doi-asserted-by":"publisher","first-page":"178","DOI":"10.1002\/JIMD.12039","volume":"42","author":"G Jacomelli","year":"2019","unstructured":"Jacomelli G, Baldini E, Mugnaini C et al (2019) Inhibiting PNP for the therapy of hyperuricemia in Lesch\u2013Nyhan disease: preliminary in vitro studies with analogues of immucillin-G. J Inherit Metab Dis 42:178\u2013185. https:\/\/doi.org\/10.1002\/JIMD.12039","journal-title":"J Inherit Metab Dis"},{"key":"1644_CR27","doi-asserted-by":"publisher","DOI":"10.1007\/s12015-024-10821-4","author":"S Javed","year":"2024","unstructured":"Javed S, Fersini M, Bernardini G (2024) Unleashing the power of induced pluripotent stem cells in in vitro modelling of Lesch\u2013Nyhan disease. Stem Cell Rev Rep. https:\/\/doi.org\/10.1007\/s12015-024-10821-4","journal-title":"Stem Cell Rev Rep"},{"key":"1644_CR28","doi-asserted-by":"publisher","first-page":"1201","DOI":"10.1093\/BRAIN\/AWL056","volume":"129","author":"HA Jinnah","year":"2006","unstructured":"Jinnah HA, Visser JE, Harris JC et al (2006) Delineation of the motor disorder of Lesch\u2013Nyhan disease. Brain 129:1201\u20131217. https:\/\/doi.org\/10.1093\/BRAIN\/AWL056","journal-title":"Brain"},{"key":"1644_CR29","doi-asserted-by":"publisher","first-page":"671","DOI":"10.1093\/brain\/awq013","volume":"133","author":"HA Jinnah","year":"2010","unstructured":"Jinnah HA, Ceballos-Picot I, Torres RJ et al (2010) Attenuated variants of Lesch\u2013Nyhan disease. Brain 133:671\u2013689. https:\/\/doi.org\/10.1093\/brain\/awq013","journal-title":"Brain"},{"key":"1644_CR30","doi-asserted-by":"publisher","DOI":"10.1155\/2013\/434010","author":"G Kleiner","year":"2013","unstructured":"Kleiner G, Marcuzzi A, Zanin V et al (2013) Cytokine levels in the serum of healthy subjects. Mediators Inflamm. https:\/\/doi.org\/10.1155\/2013\/434010","journal-title":"Mediators Inflamm"},{"key":"1644_CR31","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/srep13887","volume":"5","author":"S Liu","year":"2015","unstructured":"Liu S, Zhou Z, Wang C et al (2015) Associations between interleukin and interleukin receptor gene polymorphisms and risk of gout. Sci Rep 5:1\u20137. https:\/\/doi.org\/10.1038\/srep13887","journal-title":"Sci Rep"},{"key":"1644_CR32","doi-asserted-by":"publisher","DOI":"10.1088\/1748-6041\/10\/4\/045012","author":"M Lorenzetti","year":"2015","unstructured":"Lorenzetti M, Bernardini G, Luxbacher T et al (2015) Surface properties of nanocrystalline TiO2\u2009coatings in relation to the in vitro plasma protein adsorption. Biomed Mater (Bristol). https:\/\/doi.org\/10.1088\/1748-6041\/10\/4\/045012","journal-title":"Biomed Mater (Bristol)"},{"key":"1644_CR33","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1016\/j.ymgme.2019.06.001","volume":"127","author":"A Madeo","year":"2019","unstructured":"Madeo A, Di Rocco M, Brassier A et al (2019) Clinical, biochemical and genetic characteristics of a cohort of 101 French and Italian patients with HPRT deficiency. Mol Genet Metab 127:147\u2013157. https:\/\/doi.org\/10.1016\/j.ymgme.2019.06.001","journal-title":"Mol Genet Metab"},{"key":"1644_CR34","doi-asserted-by":"publisher","DOI":"10.1016\/j.ddmod.2019.10.004","author":"V Micheli","year":"2020","unstructured":"Micheli V, Jacomelli G, Santucci A, Bernardini G (2020) Animal and cell models for Lesch\u2013Nyhan syndrome. Drug Discov Today Dis Models. https:\/\/doi.org\/10.1016\/j.ddmod.2019.10.004","journal-title":"Drug Discov Today Dis Models"},{"key":"1644_CR35","doi-asserted-by":"publisher","first-page":"1","DOI":"10.26508\/lsa.202403191","volume":"8","author":"L Monteiro","year":"2025","unstructured":"Monteiro L, de Archambault B, Starchuk AS LF, et al (2025) Inhibition of Xanthine oxidoreductase with febuxostat, but not allopurinol, prevents inflammasome assembly and IL-1\u03b2 release. Life Sci Alliance 8:1\u201311. https:\/\/doi.org\/10.26508\/lsa.202403191","journal-title":"Life Sci Alliance"},{"key":"1644_CR36","doi-asserted-by":"publisher","first-page":"i260","DOI":"10.1093\/ECCO-JCC\/JJAD212.0141","volume":"18","author":"A Petrillo","year":"2024","unstructured":"Petrillo A, Di, Onali S, Era B et al (2024) P011 altered expression and enzymatic activity of Xanthine oxidase in inflammatory bowel disease. J Crohns Colitis 18:i260\u2013i260. https:\/\/doi.org\/10.1093\/ECCO-JCC\/JJAD212.0141","journal-title":"J Crohns Colitis"},{"key":"1644_CR37","doi-asserted-by":"publisher","DOI":"10.1155\/2021\/1653392","volume":"2021","author":"IP Pratomo","year":"2021","unstructured":"Pratomo IP, Noor DR, Kusmardi K et al (2021) Xanthine oxidase-induced inflammatory responses in respiratory epithelial cells: a review in immunopathology of COVID-19. Int J Inflam 2021:1653392. https:\/\/doi.org\/10.1155\/2021\/1653392","journal-title":"Int J Inflam"},{"key":"1644_CR38","doi-asserted-by":"publisher","first-page":"1432","DOI":"10.1038\/sj.mt.6300199","volume":"15","author":"S Song","year":"2007","unstructured":"Song S, Friedmann T (2007) Tissue-specific aberrations of gene expression in HPRT-deficient mice: functional complexity in a monogenic disease? Mol Ther 15:1432\u20131443. https:\/\/doi.org\/10.1038\/sj.mt.6300199","journal-title":"Mol Ther"},{"key":"1644_CR39","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1016\/j.mcn.2012.08.009","volume":"53","author":"HB Stolp","year":"2013","unstructured":"Stolp HB (2013) Neuropoietic cytokines in normal brain development and neurodevelopmental disorders. Mol Cell Neurosci 53:63\u201368. https:\/\/doi.org\/10.1016\/j.mcn.2012.08.009","journal-title":"Mol Cell Neurosci"},{"key":"1644_CR40","doi-asserted-by":"publisher","first-page":"8523","DOI":"10.1038\/S41598-021-87955-9","volume":"11","author":"DJ Sutcliffe","year":"2021","unstructured":"Sutcliffe DJ, Dinasarapu AR, Visser JE et al (2021) Induced pluripotent stem cells from subjects with Lesch\u2013Nyhan disease. Sci Rep 11:8523. https:\/\/doi.org\/10.1038\/S41598-021-87955-9","journal-title":"Sci Rep"},{"key":"1644_CR41","doi-asserted-by":"publisher","first-page":"D638","DOI":"10.1093\/NAR\/GKAC1000","volume":"51","author":"D Szklarczyk","year":"2023","unstructured":"Szklarczyk D, Kirsch R, Koutrouli M et al (2023) The STRING database in 2023: protein-protein association networks and functional enrichment analyses for any sequenced genome of interest. Nucleic Acids Res 51:D638\u2013D646. https:\/\/doi.org\/10.1093\/NAR\/GKAC1000","journal-title":"Nucleic Acids Res"},{"key":"1644_CR42","doi-asserted-by":"publisher","first-page":"1460","DOI":"10.1002\/aur.1803","volume":"10","author":"N Szoko","year":"2017","unstructured":"Szoko N, McShane AJ, Natowicz MR (2017) Proteomic explorations of autism spectrum disorder. Autism Res 10:1460\u20131469. https:\/\/doi.org\/10.1002\/aur.1803","journal-title":"Autism Res"},{"key":"1644_CR43","doi-asserted-by":"publisher","first-page":"349","DOI":"10.1080\/21678707.2019.1652597","volume":"7","author":"RJ Torres","year":"2019","unstructured":"Torres RJ (2019) Current understanding of Lesch\u2013Nyhan disease and potential therapeutic targets. Expert Opin Orphan Drugs 7:349\u2013361. https:\/\/doi.org\/10.1080\/21678707.2019.1652597","journal-title":"Expert Opin Orphan Drugs"},{"key":"1644_CR44","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1186\/1750-1172-2-48","volume":"2","author":"RJ Torres","year":"2007","unstructured":"Torres RJ, Puig JG (2007) Hypoxanthine-guanine phosophoribosyltransferase (HPRT) deficiency: Lesch\u2013Nyhan syndrome. Orphanet J Rare Dis 2:48. https:\/\/doi.org\/10.1186\/1750-1172-2-48","journal-title":"Orphanet J Rare Dis"},{"key":"1644_CR45","doi-asserted-by":"publisher","first-page":"1109","DOI":"10.1007\/s10545-015-9854-4","volume":"38","author":"RJ Torres","year":"2015","unstructured":"Torres RJ, Puig JG (2015) Hypoxanthine deregulates genes involved in early neuronal development. Implications in Lesch\u2013Nyhan disease pathogenesis. J Inherit Metab Dis 38:1109\u20131118. https:\/\/doi.org\/10.1007\/s10545-015-9854-4","journal-title":"J Inherit Metab Dis"},{"key":"1644_CR46","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-022-04326-x","author":"JS Witteveen","year":"2022","unstructured":"Witteveen JS, Loopstok SR, Ballesteros LL et al (2022) HGprt deficiency disrupts dopaminergic circuit development in a genetic mouse model of Lesch\u2013Nyhan disease. Cell Mol Life Sci. https:\/\/doi.org\/10.1007\/s00018-022-04326-x","journal-title":"Cell Mol Life Sci"},{"key":"1644_CR47","doi-asserted-by":"publisher","DOI":"10.7717\/PEERJ.14554","volume":"11","author":"X Wu","year":"2023","unstructured":"Wu X, You C (2023) The biomarkers discovery of hyperuricemia and gout: proteomics and metabolomics. PeerJ 11:e14554. https:\/\/doi.org\/10.7717\/PEERJ.14554","journal-title":"PeerJ"},{"key":"1644_CR48","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1016\/J.NEULET.2010.05.063","volume":"479","author":"X Zhao","year":"2010","unstructured":"Zhao X, Xiao WZ, Pu XP, Zhong LJ (2010) Proteome analysis of the sera from Chinese parkinson\u2019s disease patients. Neurosci Lett 479:175\u2013179. https:\/\/doi.org\/10.1016\/J.NEULET.2010.05.063","journal-title":"Neurosci Lett"}],"container-title":["Cellular and Molecular Neurobiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10571-025-01644-z.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s10571-025-01644-z","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10571-025-01644-z.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T05:42:03Z","timestamp":1768369323000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s10571-025-01644-z"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,15]]},"references-count":48,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["1644"],"URL":"https:\/\/doi.org\/10.1007\/s10571-025-01644-z","relation":{},"ISSN":["1573-6830"],"issn-type":[{"value":"1573-6830","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,15]]},"assertion":[{"value":"20 August 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 November 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 December 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}],"article-number":"16"}}