{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T09:19:10Z","timestamp":1785403150499,"version":"3.56.0"},"reference-count":63,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,5,17]],"date-time":"2026-05-17T00:00:00Z","timestamp":1778976000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001807","name":"State of S\u00e3o Paulo Research Foundation","doi-asserted-by":"publisher","award":["2025\/09071-5"],"award-info":[{"award-number":["2025\/09071-5"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"award":["2025\/09071-5"],"award-info":[{"award-number":["2025\/09071-5"]}],"id":[{"id":"https:\/\/ror.org\/02ddkpn78","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002322","name":"Coordination for the Improvement of Higher Education Personnel","doi-asserted-by":"crossref","award":["001"],"award-info":[{"award-number":["001"]}],"id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medical Sciences"],"abstract":"<jats:p>Background\/Objectives: Parkinson\u2019s disease (PD) is a progressive neurodegenerative disorder characterized by complex and interconnected pathophysiological mechanisms, including mitochondrial dysfunction, oxidative stress, neuroinflammation, lysosomal impairment, and altered neurotransmitter metabolism. Unlike cerebrospinal fluid or blood, urine offers a truly non-invasive source of biomarkers, reflecting systemic metabolic changes and renal protein excretion linked to neurodegeneration. This review aims to critically synthesize current evidence on urinary biomarkers in PD and to organize this heterogeneous literature into pathophysiologically meaningful domains. Methods: A comprehensive literature search of human studies investigating urinary biomarkers in PD was performed. Eligible studies were comprehensively analyzed and classified according to dominant biological pathways. To facilitate interpretation, findings were organized into six thematic domains: genetic and protein-based biomarkers; metabolic pathways and mitochondrial dysfunction; oxidative stress and neuroinflammation; gut\u2013brain-axis-related metabolites; hormonal and systemic biomarkers; and emerging exploratory markers. Results were summarized in domain-specific tables and integrated using a conceptual framework. Results: A total of 32 human studies met the inclusion criteria, revealing diverse urinary molecular signatures associated with PD across multiple biological domains. Genetic and protein-based markers, including LRRK2-related proteins, \u03b1-synuclein species, and lysosomal lipids, showed potential for disease stratification. Metabolomic studies consistently identified alterations in acylcarnitines, organic acids, and amino acid metabolism, reflecting mitochondrial dysfunction. Biomarkers related to oxidative stress, immune activation, gut microbiota metabolism, and hormonal regulation further highlighted the systemic nature of PD. However, most individual biomarkers lacked disease specificity and exhibited methodological heterogeneity. Conclusions: Current evidence supports urine as a valuable source of systemic biomarkers reflecting multiple pathophysiological processes in PD. While single urinary markers remain insufficient for clinical application, integrated omics-based approaches\u2014particularly metabolomics and peptidomics\/proteomics\u2014hold promise for identifying combinatorial biomarker signatures. Future longitudinal and standardized studies are required to enhance specificity and translational potential for non-invasive diagnosis and disease monitoring in PD.<\/jats:p>","DOI":"10.3390\/medsci14020258","type":"journal-article","created":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T10:25:16Z","timestamp":1779099916000},"page":"258","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Urinary Biomarkers in Parkinson\u2019s Disease: A Structured Integrative Review of Pathophysiological Pathways"],"prefix":"10.3390","volume":"14","author":[{"given":"Halyne Queiroz Pantale\u00e3o","family":"Santos","sequence":"first","affiliation":[{"name":"Natural and Humanities Sciences Center (CCNH), Experimental Morphophysiology Laboratory, Federal University of ABC (UFABC), S\u00e3o Bernardo do Campo 09606-070, SP, Brazil"},{"name":"Central Laboratory Division, Hospital das Cl\u00ednicas da Faculdade de Medicina, Universidade de S\u00e3o Paulo (HCFMUSP), LIM-03, S\u00e3o Paulo 05403-010, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nairo Massakazu","family":"Sumita","sequence":"additional","affiliation":[{"name":"Central Laboratory Division, Hospital das Cl\u00ednicas da Faculdade de Medicina, Universidade de S\u00e3o Paulo (HCFMUSP), LIM-03, S\u00e3o Paulo 05403-010, SP, Brazil"}],"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":"Natural and Humanities Sciences Center (CCNH), Experimental Morphophysiology Laboratory, Federal University of 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":"Mathematics, Computation and Cognition Center (CMCC), Federal University of ABC (UFABC), S\u00e3o Bernardo do Campo 09606-070, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1038\/s41746-024-01217-2","article-title":"Digital Biomarkers for Precision Diagnosis and Monitoring in Parkinson\u2019s Disease","volume":"7","author":"Sun","year":"2024","journal-title":"npj Digit. 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