{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T19:49:26Z","timestamp":1785354566320,"version":"3.55.0"},"reference-count":49,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,4,4]],"date-time":"2025-04-04T00:00:00Z","timestamp":1743724800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100009708","name":"Novo Nordisk Fonden","doi-asserted-by":"publisher","award":["NNF20OC0061575"],"award-info":[{"award-number":["NNF20OC0061575"]}],"id":[{"id":"10.13039\/501100009708","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["406936\/2023\u20104"],"award-info":[{"award-number":["406936\/2023\u20104"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["309965\/2022\u20105"],"award-info":[{"award-number":["309965\/2022\u20105"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["406792\/2022\u20104"],"award-info":[{"award-number":["406792\/2022\u20104"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["407966\/2021\u20108"],"award-info":[{"award-number":["407966\/2021\u20108"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["402653\/20181"],"award-info":[{"award-number":["402653\/20181"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002322","name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior","doi-asserted-by":"publisher","award":["88881.700905\/2022\u201001"],"award-info":[{"award-number":["88881.700905\/2022\u201001"]}],"id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004901","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de Minas Gerais","doi-asserted-by":"publisher","award":["BPD\u201000133\u201022"],"award-info":[{"award-number":["BPD\u201000133\u201022"]}],"id":[{"id":"10.13039\/501100004901","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Proteomics Clinical Apps"],"published-print":{"date-parts":[[2025,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Purpose<\/jats:title><jats:p>Parkinson's disease (PD) is neuropathologically characterized by the progressive degeneration of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNpc), affecting 10 million people worldwide. Rosmarinic acid (RA), a polyphenol found in plants like rosemary (<jats:italic>Rosmarinus officinalis<\/jats:italic>), is known for its intriguing biological properties and potential antioxidant and neuroprotective effects. In a previous study we showed that RA treatment prevented hyperlocomotion in mice with MPTP (1\u2010methyl\u20104\u2010phenyl\u20101,2,3,6\u2010tetrahydropyridine)\u2010induced parkinsonism and improved the monoaminergic system in healthy animals. However, the molecular mechanisms underlying RA's action in PD remain unclear.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental design<\/jats:title><jats:p>In this study, we treated MPTP\u2010induced PD animals (C57BL\/6 male mice) with RA orally at a dose of 100\u00a0mg\/kg for 15 days and examined the proteome of substantia nigra (SN) to identify possible regulatory targets of RA treatment to shed some lights into its neuroprotective effects.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Quantitative proteomics revealed that RA treatment regulated proteins associated with oxidative phosphorylation (OXPHOS), glutamatergic synapse, and vesicular cycle signaling pathway. We identified 371 proteins significantly regulated in response to RA administration (255 upregulated and 116 downregulated). Notably, some cellular targets of RA treatment reported here, including mGluR2\/mGluR3\/EAAT\u2014proteins from the glutamatergic system\u2014and proteins from the Complex I of the electron transport chain are promising targets for therapeutic intervention.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and clinical relevance<\/jats:title><jats:p>These findings highlight the molecular differences between MPTP\u2010induced PD mice and those treated with RA, providing insights on the molecular basis behind the neuroprotective effects of RA and revealing potential PD signatures that warrant further investigation.<\/jats:p><\/jats:sec>","DOI":"10.1002\/prca.70006","type":"journal-article","created":{"date-parts":[[2025,4,5]],"date-time":"2025-04-05T12:32:43Z","timestamp":1743856363000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Proteomic Analysis of Substantia Nigra Reveals Molecular Insights Into the Neuroprotection Effect of Rosmarinic Acid Treatment in MPTP\u2010Induced Mouse Model of Parkinson's Disease"],"prefix":"10.1002","volume":"19","author":[{"given":"Sarah Martins","family":"Presti\u2010Silva","sequence":"first","affiliation":[{"name":"Postgraduate Program in Biochemistry and Immunology Federal University of Minas Gerais  Belo Horizonte Minas Gerais Brazil"},{"name":"Department of Physiological Science Federal University of Espirito Santo, Vitoria  Espirito Santo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucas","family":"Rodrigues\u2010Ribeiro","sequence":"additional","affiliation":[{"name":"Postgraduate Program in Biochemistry and Immunology Federal University of Minas Gerais  Belo Horizonte Minas Gerais Brazil"},{"name":"National Institute of Science and Technology in Nanobiopharmaceutics (INCT\u2010Nanobiofar) Department of Physiology and Biophysics Federal University of Minas Gerais  Belo Horizonte Minas Gerais Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vladimir","family":"Gorshkov","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology University of Sourthern Denmark  Odense Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Kjeldsen","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology University of Sourthern Denmark  Odense Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thiago","family":"Verano\u2010Braga","sequence":"additional","affiliation":[{"name":"Postgraduate Program in Biochemistry and Immunology Federal University of Minas Gerais  Belo Horizonte Minas Gerais Brazil"},{"name":"National Institute of Science and Technology in Nanobiopharmaceutics (INCT\u2010Nanobiofar) Department of Physiology and Biophysics Federal University of Minas Gerais  Belo Horizonte Minas Gerais Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4739-8349","authenticated-orcid":false,"given":"Rita Gomes Wanderley","family":"Pires","sequence":"additional","affiliation":[{"name":"Postgraduate Program in Biochemistry and Immunology Federal University of Minas Gerais  Belo Horizonte Minas Gerais Brazil"},{"name":"Department of Physiological Science Federal University of Espirito Santo, Vitoria  Espirito Santo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,4,4]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0837\u201006.2006"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0969\u20109961(03)00037\u20108"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2010.08.037"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn.2016.178"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M503483200"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurol.2017.08.005"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471\u20102091\u20108\u2010S1\u2010S13"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.10483"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jphs.2020.07.011"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd.2018.136"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1055\/s\u20100035\u20101568274"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00210-020-01935-w"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1039\/C0FO00070A"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/ptr.904"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476\u20105381.2009.00213.x"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1177\/1091581810383705"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2022.859978"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12031\u2010009\u20109182\u2010y"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1021\/acschemneuro.0c00375"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2022.114257"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2016.03.041"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12031\u2010016\u20100831\u20107"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2021.114210"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pnpbp.2009.03.004"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ab.2019.05.006"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkac194"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.1239303"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1155\/2017\/9349487"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awab378"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbabio.2016.02.012"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature13909"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471\u20104159.1990.tb02325.x"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40478\u2010022\u201001424\u20106"},{"key":"e_1_2_11_35_1","volume-title":"Fundamentals of Biochemistry: Life at the Molecular Level","author":"Voet D.","year":"2013"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2123090119"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392\u2010022\u201000983\u20103"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awq132"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines10092278"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnsyn.2016.00007"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/362318a0"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1002\/pmic.200700955"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2019.04.052"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2022.108275"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/0896\u20106273(92)90118\u2010w"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.20\u201009\u201003085.2000"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0163\u20107258(00)00098\u2010x"},{"key":"e_1_2_11_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0091\u20103057(02)00842\u20100"},{"key":"e_1_2_11_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2003.08.032"},{"key":"e_1_2_11_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coph.2018.03.003"}],"container-title":["PROTEOMICS \u2013 Clinical Applications"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/prca.70006","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,13]],"date-time":"2025-05-13T01:39:53Z","timestamp":1747100393000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/prca.70006"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,4]]},"references-count":49,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2025,5]]}},"alternative-id":["10.1002\/prca.70006"],"URL":"https:\/\/doi.org\/10.1002\/prca.70006","archive":["Portico"],"relation":{},"ISSN":["1862-8346","1862-8354"],"issn-type":[{"value":"1862-8346","type":"print"},{"value":"1862-8354","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,4]]},"assertion":[{"value":"2024-07-18","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-03-14","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-04-04","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70006"}}