{
    "abstract": "The pathobiology of restless legs syndrome (RLS) remains poorly understood, complicating effective treatment. This observational cross-sectional study aimed to identify a cerebrospinal fluid proteomic signature of RLS and to explore sex-specific differences in cerebrospinal fluid proteomics.\nCerebrospinal fluid samples were collected from 22 untreated RLS patients and 18 controls, matched for age, body mass index, and sex. Proteomic analysis was conducted using the SOMAscan\u00ae platform, assessing over 7,000 peptides.\nEight proteins were differentially abundant between patients and controls, with CRP and JAML increased, and TAPBPL and IL1RL1 decreased. Pathway analysis highlighted significant involvement in immune response, coagulation, and cytoskeletal regulation. Analyses were then carried out with sex stratification, comparing separately men and women. Sex-specific analyses revealed more pronounced proteomic alterations in males (68 differentially abundant proteins vs. control males) than females (17 proteins). Gene enrichment analysis revealed that men with RLS had more involvement of gene regulation and epigenetic factors than control males and women with restless legs syndrome had greater involvement of systemic inflammatory and vascular processes than control females.\nThis study identified a cerebrospinal fluid proteomic signature in RLS, implicating immune and inflammatory pathways in the disease's pathophysiology. Significant sex differences in protein level suggest potential sex-specific mechanisms in RLS, warranting further investigation. These findings contribute to the current understanding of RLS and could inform future therapeutic strategies.",
    "authors": [
        {
            "affiliation": "Vita-Salute San Raffaele University, 20132 Milan, Italy.\nSan Raffaele Scientific Institute, Division of Neuroscience, Sleep Disorders Center, 20127 Milan, Italy.",
            "firstname": "Maria P",
            "initials": "MP",
            "lastname": "Mogavero"
        },
        {
            "affiliation": "Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA.",
            "firstname": "Gang",
            "initials": "G",
            "lastname": "Peng"
        },
        {
            "affiliation": "Genomix4Life Srl, 84081 Baronissi, Italy.\nGenome Research Center for Health-CRGS, 84081 Baronissi, Italy.",
            "firstname": "Giovanna",
            "initials": "G",
            "lastname": "Marchese"
        },
        {
            "affiliation": "Clinical Neurophysiology Research Unit, Oasi Research Institute-IRCCS, 94018 Troina, Italy.\nDepartment of Surgery and Medical-Surgical Specialties, University of Catania, 95123 Catania, Italy.",
            "firstname": "Giuseppe",
            "initials": "G",
            "lastname": "Lanza"
        },
        {
            "affiliation": "Vita-Salute San Raffaele University, 20132 Milan, Italy.\nSan Raffaele Scientific Institute, Division of Neuroscience, Sleep Disorders Center, 20127 Milan, Italy.",
            "firstname": "Luigi",
            "initials": "L",
            "lastname": "Ferini-Strambi"
        },
        {
            "affiliation": "Clinical Neurophysiology Research Unit, Oasi Research Institute-IRCCS, 94018 Troina, Italy.",
            "firstname": "Raffaele",
            "initials": "R",
            "lastname": "Ferri"
        },
        {
            "affiliation": "Department of Neurology, Yale University, New Haven, CT, USA.\nDepartment of Neurology, Connecticut Veterans Affairs Healthcare System, West Haven, CT, USA.",
            "firstname": "Brian B",
            "initials": "BB",
            "lastname": "Koo"
        }
    ],
    "conclusions": null,
    "copyrights": "\u00a9 The Author(s) 2025. Published by Oxford University Press on behalf of Sleep Research Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site\u2014for further information please contact journals.permissions@oup.com.",
    "doi": "10.1093/sleep/zsaf112",
    "journal": "Sleep",
    "keywords": [
        "Cerebrospinal fluid",
        "Differential peptide expression",
        "Immune and inflammatory pathways",
        "Proteomics",
        "Restless Legs Syndrome",
        "Sex-specific differences"
    ],
    "methods": null,
    "publication_date": "2025-04-28",
    "pubmed_id": "40289925",
    "results": "Eight proteins were differentially abundant between patients and controls, with CRP and JAML increased, and TAPBPL and IL1RL1 decreased. Pathway analysis highlighted significant involvement in immune response, coagulation, and cytoskeletal regulation. Analyses were then carried out with sex stratification, comparing separately men and women. Sex-specific analyses revealed more pronounced proteomic alterations in males (68 differentially abundant proteins vs. control males) than females (17 proteins). Gene enrichment analysis revealed that men with RLS had more involvement of gene regulation and epigenetic factors than control males and women with restless legs syndrome had greater involvement of systemic inflammatory and vascular processes than control females.",
    "title": "Sex Differences in Cerebrospinal Fluid Proteomics of Patients with Restless Legs Syndrome.",
    "xml": "<Element 'PubmedArticle' at 0x788506815620>"
}