{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T14:29:47Z","timestamp":1785421787321,"version":"3.56.0"},"reference-count":66,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T00:00:00Z","timestamp":1784764800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003196","name":"Ministero della Salute","doi-asserted-by":"publisher","award":["\u201cRicerca Corrente\u201d [RC No. 2800946]"],"award-info":[{"award-number":["\u201cRicerca Corrente\u201d [RC No. 2800946]"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]},{"award":["\u201cRicerca Corrente\u201d [RC No. 2800946]"],"award-info":[{"award-number":["\u201cRicerca Corrente\u201d [RC No. 2800946]"]}],"id":[{"id":"https:\/\/ror.org\/00789fa95","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Restless legs syndrome (RLS) and RLS-like symptoms are frequently reported in Parkinson\u2019s disease (PD), but whether this clinical overlap reflects shared biology or convergent symptom expression remains uncertain. We performed an exploratory comparative analysis of peripheral blood mononuclear cell RNA-seq data from 17 drug-free patients with RLS and 60 patients with PD, most of whom were receiving dopaminergic treatment. Because the two cohorts were derived from independent datasets and no healthy control group was included, all findings were interpreted as relative PD-versus-RLS differences rather than disease-specific alterations. Differential expression and pathway analyses identified broad transcriptomic separation between the two groups. Genes with relatively higher expression in PD than RLS included transcripts related to dopamine metabolism, tetrahydrobiopterin biology, iron transport, oxidative stress, and inflammatory signaling, whereas genes with relatively higher expression in RLS than PD involved iron\/ferroptosis-related biology, GPCR-mediated signaling, synaptic modulation, and circadian-related pathways. These results suggest that peripheral blood transcriptomics may help generate hypotheses on the biological heterogeneity underlying RLS-like symptoms in PD. However, because of treatment imbalance, cohort differences, batch-group confounding, absence of healthy controls, and the use of PBMCs as a peripheral tissue, the findings should be considered hypothesis-generating and require independent validation.<\/jats:p>","DOI":"10.3390\/ijms27156576","type":"journal-article","created":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T17:13:17Z","timestamp":1784826797000},"page":"6576","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Comparative Peripheral Blood Transcriptomic Profiles in Parkinson\u2019s Disease and Restless Legs Syndrome: An Exploratory Between-Cohort Analysis"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6662-2281","authenticated-orcid":false,"given":"Maria P.","family":"Mogavero","sequence":"first","affiliation":[{"name":"Oasi Research Institute-IRCCS, 94018 Troina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanna","family":"Marchese","sequence":"additional","affiliation":[{"name":"Genomix4Life Srl, 84081 Baronissi, Italy"},{"name":"Genome Research Center for Health (CRGS), 84081 Baronissi, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8801-564X","authenticated-orcid":false,"given":"Giovanna M.","family":"Ventola","sequence":"additional","affiliation":[{"name":"Genomix4Life Srl, 84081 Baronissi, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5659-662X","authenticated-orcid":false,"given":"Giuseppe","family":"Lanza","sequence":"additional","affiliation":[{"name":"Oasi Research Institute-IRCCS, 94018 Troina, Italy"},{"name":"Department of General Surgery and Medical-Surgical Specialties, University of Catania, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2616-0558","authenticated-orcid":false,"given":"Stefan","family":"Clemens","sequence":"additional","affiliation":[{"name":"Department of Physiology, Brody School of Medicine, East Carolina University, Greenville, NC 27834, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele","family":"Salemi","sequence":"additional","affiliation":[{"name":"Oasi Research Institute-IRCCS, 94018 Troina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2207-1398","authenticated-orcid":false,"given":"Oliviero","family":"Bruni","sequence":"additional","affiliation":[{"name":"Department of Human Neuroscience, Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6937-3065","authenticated-orcid":false,"given":"Raffaele","family":"Ferri","sequence":"additional","affiliation":[{"name":"Oasi Research Institute-IRCCS, 94018 Troina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1016\/j.sleep.2014.03.025","article-title":"Restless legs syndrome\/Willis-Ekbom disease diagnostic criteria: Updated International Restless Legs Syndrome Study Group (IRLSSG) consensus criteria\u2013history, rationale, description, and significance","volume":"15","author":"Allen","year":"2014","journal-title":"Sleep Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1038\/nrneurol.2010.55","article-title":"Restless legs syndrome: Pathophysiology, clinical presentation and management","volume":"6","author":"Trenkwalder","year":"2010","journal-title":"Nat. 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