{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T14:14:03Z","timestamp":1779804843865,"version":"3.53.1"},"reference-count":39,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,5,3]],"date-time":"2026-05-03T00:00:00Z","timestamp":1777766400000},"content-version":"vor","delay-in-days":2,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100017610","name":"Shenzhen Science and Technology Innovation Program","doi-asserted-by":"publisher","award":["JCYJ20220818102206014"],"award-info":[{"award-number":["JCYJ20220818102206014"]}],"id":[{"id":"10.13039\/501100017610","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82271454"],"award-info":[{"award-number":["82271454"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CNS Neurosci Ther"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>We aimed to investigate the shared molecular pathways between Parkinson's disease (PD) and constipation using bioinformatics analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Differentially expressed genes (DEGs) were identified via the R limma package, and Weighted Gene Co\u2010Expression Network Analysis (WGCNA) was conducted to identify hub modules. Biological enrichment analysis clarified the biological processes involved. A gene\u2013gene interaction (GGI) network was constructed to identify shared hub biomarkers. Validation of these biomarkers was done in\u00a0vitro with \u03b1\u2010synuclein (\u03b1\u2010syn)\u2010treated SH\u2010SY5Y cells and in\u00a0vivo through \u03b1\u2010syn\u2010induced PD mouse models, A53T transgenic mice, and loperamide\u2010induced constipation models.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Numerous DEGs were identified in both conditions, with 14 shared DEGs found through the intersection of core modules and upregulated DEGs. These DEGs are primarily involved in energy metabolism, protein modification, and mitochondrial function. Five key hub genes were identified using the GGI network and gene topological analysis. Notably, Serine hydroxymethyltransferase 2 (SHMT2) expression was significantly upregulated after \u03b1\u2010syn treatment in\u00a0vitro. Immunohistochemical and immunofluorescence analyses revealed elevated SHMT2 expression in brain and colon tissues in PD mouse models (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001), whereas in constipation models, SHMT2 was only elevated in the colon wall with no significant expression in the enteric nervous system.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our findings offer new views on the molecular link between PD and constipation, suggesting SHMT2 as a possible biomarker and therapeutic target for PD symptoms.<\/jats:p>\n                  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