{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T02:06:09Z","timestamp":1789610769148,"version":"build-2803163510"},"reference-count":33,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T00:00:00Z","timestamp":1764115200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Health & Welfare through the Korea Health Industry Development Institute","award":["RS-2025-02263620"],"award-info":[{"award-number":["RS-2025-02263620"]}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Early detection of Parkinson\u2019s disease (PD) remains challenging due to the lack of reliable blood-based biomarkers. While microRNAs (miRNAs) show promise as circulating biomarkers, translating preclinical discoveries to clinically applicable panels requires rigorous validation across platforms and populations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We performed temporal miRNA profiling in an acute MPTP mouse model (day 0 vs. day 5,\n                      <jats:italic>n<\/jats:italic>\n                      \u202f=\u202f4 per group) using limma differential expression analysis with FDR correction. To address high-dimensional small-sample challenges, we employed global permutation testing and stability selection with elastic net regularization over 2,000 iterations. A compact miRNA panel was derived and validated in three independent human cohorts: GSE16658 (PBMC,\n                      <jats:italic>n<\/jats:italic>\n                      \u202f=\u202f32), GSE269776 (serum exosomes 2021,\n                      <jats:italic>n<\/jats:italic>\n                      \u202f=\u202f76), and GSE269775 (serum exosomes 2020,\n                      <jats:italic>n<\/jats:italic>\n                      \u202f=\u202f100). Performance was assessed using ROC analysis with permutation-based\n                      <jats:italic>p<\/jats:italic>\n                      -values.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Seventeen miRNAs showed significant time-dependent changes in MPTP-treated mice (FDR &amp;lt;0.05), with 15 down-regulated and 2 up-regulated at day 5. Stability selection identified a 6-miRNA panel comprising miR-92b, miR-133a, miR-326, miR-125b, miR-148a, and miR-30b. External validation demonstrated consistent discriminative performance across platforms: GSE16658 AUC\u202f=\u202f0.696 (\n                      <jats:italic>p<\/jats:italic>\n                      \u202f=\u202f0.060), GSE269776 AUC\u202f=\u202f0.791 (\n                      <jats:italic>p<\/jats:italic>\n                      \u202f&amp;lt;\u202f0.001), and GSE269775 AUC\u202f=\u202f0.725 (\n                      <jats:italic>p<\/jats:italic>\n                      \u202f&amp;lt;\u202f0.001).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>The signature showed platform-agnostic stability, performing comparably in PBMC and serum exosomes despite biological and technical differences. A 6-miRNA signature derived from acute MPTP response translates effectively to human blood samples, demonstrating reproducible PD discrimination across multiple platforms. The compact panel size and cross-platform compatibility support its potential for clinical biomarker development. By integrating AI-enhanced feature selection and permutation-based validation, this study provides a reproducible framework for biomarker discovery and a foundation for future early detection and precision medicine in Parkinson\u2019s disease.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fneur.2025.1704976","type":"journal-article","created":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T05:16:07Z","timestamp":1764134167000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Cross-species validation of a 6-miRNA blood signature for Parkinson\u2019s disease: from MPTP mice to human PBMC and serum exosomes"],"prefix":"10.3389","volume":"16","author":[{"given":"Nagyum","family":"Jung","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seung-Nam","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,11,26]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1016\/S0140-6736(23)01419-8","article-title":"The epidemiology of Parkinson\u2019s disease","volume":"403","author":"Ben-Shlomo","year":"2024","journal-title":"Lancet"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"663","DOI":"10.1007\/s00702-024-02774-2","article-title":"Current trends in basic research on Parkinson\u2019s disease: from mitochondria, lysosome to \u03b1-synuclein","volume":"131","author":"Matsui","year":"2024","journal-title":"J Neural Transm 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