{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:49:25Z","timestamp":1787028565156,"version":"build-2736575974"},"reference-count":80,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2025,7,15]],"date-time":"2025-07-15T00:00:00Z","timestamp":1752537600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001807","name":"S\u00e3o Paulo Research Foundation","doi-asserted-by":"publisher","award":["2023\/03608-1"],"award-info":[{"award-number":["2023\/03608-1"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"S\u00e3o Paulo Research Foundation","doi-asserted-by":"publisher","award":["2024\/10831-1"],"award-info":[{"award-number":["2024\/10831-1"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"S\u00e3o Paulo Research Foundation","doi-asserted-by":"publisher","award":["2024\/02247-8"],"award-info":[{"award-number":["2024\/02247-8"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"S\u00e3o Paulo Research Foundation","doi-asserted-by":"publisher","award":["001"],"award-info":[{"award-number":["001"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Coordination for the Improvement of Higher Education Personnel","award":["2023\/03608-1"],"award-info":[{"award-number":["2023\/03608-1"]}]},{"name":"Coordination for the Improvement of Higher Education Personnel","award":["2024\/10831-1"],"award-info":[{"award-number":["2024\/10831-1"]}]},{"name":"Coordination for the Improvement of Higher Education Personnel","award":["2024\/02247-8"],"award-info":[{"award-number":["2024\/02247-8"]}]},{"name":"Coordination for the Improvement of Higher Education Personnel","award":["001"],"award-info":[{"award-number":["001"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Zebrafish (Danio rerio) combine accessible behavioral phenotypes with conserved neurochemical pathways and molecular features of vertebrate brain function, positioning them as a powerful model for investigating early neurodegenerative processes and screening neuroprotective strategies. In this context, integrated behavioral and proteomic analyses provide valuable insights into the initial pathophysiological events shared by conditions such as Parkinson\u2019s disease and related disorders\u2014including mitochondrial dysfunction, oxidative stress, and synaptic impairment\u2014which emerge before overt neuronal loss and offer a crucial window to understand disease progression and evaluate therapeutic candidates prior to irreversible damage. To investigate this early window of dysfunction, zebrafish larvae were exposed to 500 \u03bcM 1-methyl-4-phenylpyridinium (MPP+) from 1 to 5 days post-fertilization and evaluated through integrated behavioral and label-free proteomic analyses. MPP+-treated larvae exhibited hypokinesia, characterized by significantly reduced total distance traveled, fewer movement bursts, prolonged immobility, and a near-complete absence of light-evoked responses\u2014mirroring features of early Parkinsonian-like motor dysfunction. Label-free proteomic profiling revealed 40 differentially expressed proteins related to mitochondrial metabolism, redox regulation, proteasomal activity, and synaptic organization. Enrichment analysis indicated broad molecular alterations, including pathways such as mitochondrial translation and vesicle-mediated transport. A focused subset of Parkinsonism-related proteins\u2014such as DJ-1 (PARK7), succinate dehydrogenase (SDHA), and multiple 26S proteasome subunits\u2014exhibited coordinated dysregulation, as visualized through protein\u2013protein interaction mapping. The upregulation of proteasome components and antioxidant proteins suggests an early-stage stress response, while the downregulation of mitochondrial enzymes and synaptic regulators reflects canonical PD-related neurodegeneration. Together, these findings provide a comprehensive functional and molecular characterization of MPP+-induced neurotoxicity in zebrafish larvae, supporting its use as a relevant in vivo system to investigate early-stage Parkinson\u2019s disease mechanisms and shared neurodegenerative pathways, as well as for screening candidate therapeutics in a developmentally responsive context.<\/jats:p>","DOI":"10.3390\/ijms26146762","type":"journal-article","created":{"date-parts":[[2025,7,15]],"date-time":"2025-07-15T09:45:52Z","timestamp":1752572752000},"page":"6762","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Integrated Behavioral and Proteomic Characterization of MPP+-Induced Early Neurodegeneration and Parkinsonism in Zebrafish Larvae"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4430-0905","authenticated-orcid":false,"given":"Adolfo Luis Almeida","family":"Maleski","sequence":"first","affiliation":[{"name":"Experimental Morphophysiology Laboratory, Natural and Humanities Sciences Center (CCNH), Universidade Federal do ABC (UFABC), S\u00e3o Bernardo do Campo 09606-070, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-3658-6505","authenticated-orcid":false,"given":"Felipe Assump\u00e7\u00e3o","family":"da Cunha e Silva","sequence":"additional","affiliation":[{"name":"Experimental Morphophysiology Laboratory, Natural and Humanities Sciences Center (CCNH), Universidade Federal do ABC (UFABC), S\u00e3o Bernardo do Campo 09606-070, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcela Bermudez","family":"Echeverry","sequence":"additional","affiliation":[{"name":"Laboratory of Neuropharmacology and Motor Behavior, Center for Mathematics, Computation, and Cognition (CMCC), Universidade Federal do ABC (UFABC), S\u00e3o Bernardo do Campo 09606-070, SP, Brazil"},{"name":"Neuroscience Laboratory, School of Medicine, Universidad de Santander (UDES), Bucaramanga 680006, Santander, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4519-8930","authenticated-orcid":false,"given":"Carlos","family":"Alberto-Silva","sequence":"additional","affiliation":[{"name":"Experimental Morphophysiology Laboratory, Natural and Humanities Sciences Center (CCNH), Universidade Federal do ABC (UFABC), S\u00e3o Bernardo do Campo 09606-070, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1038\/nature12111","article-title":"The Zebrafish Reference Genome Sequence and Its Relationship to the Human Genome","volume":"496","author":"Howe","year":"2013","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1016\/S0006-8993(00)03174-7","article-title":"The Teleostean (Zebrafish) Dopaminergic System Ascending to the Subpallium (Striatum) Is Located in the Basal Diencephalon (Posterior Tuberculum)","volume":"889","author":"Rink","year":"2001","journal-title":"Brain Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1002\/cne.20281","article-title":"Relationship of Tyrosine Hydroxylase and Serotonin Immunoreactivity to Sensorimotor Circuitry in Larval Zebrafish","volume":"480","author":"McLean","year":"2004","journal-title":"J. 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