{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T19:53:46Z","timestamp":1792007626033,"version":"4.4.0"},"reference-count":75,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T00:00:00Z","timestamp":1770249600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medical Sciences"],"abstract":"<jats:p>Parkinson\u2019s disease (PD) is a progressive and heterogeneous neurodegenerative disorder and one of the fastest-growing causes of neurological disability worldwide. Although historically defined by motor manifestations resulting from nigrostriatal dopaminergic degeneration, PD is now recognized as a multisystem disorder. Non-motor features\u2014including autonomic dysfunction, neuropsychiatric symptoms, cognitive impairment, and sleep-related disorders\u2014frequently precede motor onset by years or even decades, delineating a clinically meaningful prodromal phase. The aetiology of PD reflects a complex interplay between genetic susceptibility and environmental exposures. Approximately 20% of cases are linked to identifiable pathogenic variants, most commonly in LRRK2, GBA1, and SNCA, whereas the majority arise from cumulative interactions among environmental factors, lifestyle determinants, and common genetic risk variants rather than from single causal mechanisms. Despite substantial advances in understanding disease biology, current therapies remain fundamentally symptomatic. Dopaminergic pharmacotherapy and device-aided interventions improve motor function and, in selected contexts, functional outcomes, but they do not modify disease progression. Non-motor symptoms remain a dominant driver of disability and reduced quality of life. Recent conceptual frameworks propose redefining PD as a biologically defined \u03b1-synucleinopathy. Emerging biomarkers, including \u03b1-synuclein seed amplification assays in cerebrospinal fluid and peripheral tissues, offer unprecedented opportunities to define biological disease, enable early detection, and stratify patients. However, biomarker positivity currently informs diagnosis and classification rather than prognostication or therapeutic selection, and validated intermediate endpoints linking biomarker change to sustained functional benefit remain lacking. Consequently, translation into disease-modifying therapies has been constrained by late-stage intervention, reliance on clinically defined populations, limited trial generalizability, and marked global inequities in access to advanced diagnostics and treatments. This narrative review synthesizes current evidence on PD epidemiology, diagnosis, aetiology, progression, and treatment, emphasizing gene\u2013environment interactions, convergence on shared pathogenic pathways, limitations of existing therapeutic paradigms, and the as-yet unrealized potential of biologically informed precision care.<\/jats:p>","DOI":"10.3390\/medsci14010072","type":"journal-article","created":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T11:13:01Z","timestamp":1770289981000},"page":"72","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Parkinson\u2019s Disease: From Gene\u2013Environment Risk to Precision Therapy"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9982-7571","authenticated-orcid":false,"given":"Oscar","family":"Arias-Carri\u00f3n","sequence":"first","affiliation":[{"name":"Divisi\u00f3n de Neurociencias Cl\u00ednica, Instituto Nacional de Rehabilitaci\u00f3n Luis Guillermo Ibarra Ibarra, Mexico City 14389, Mexico"},{"name":"Tecnologico de Monterrey, Escuela de Medicina y Ciencias de la Salud, Mexico City 14380, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"S3","DOI":"10.3233\/JPD-181474","article-title":"The Emerging Evidence of the Parkinson Pandemic","volume":"8","author":"Dorsey","year":"2018","journal-title":"J. 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