{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T17:36:44Z","timestamp":1793036204250,"version":"4.5.0"},"reference-count":34,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T00:00:00Z","timestamp":1783641600000},"content-version":"vor","delay-in-days":9,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CNS Neurosci Ther"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Parkinson's disease (PD), a common neurodegenerative condition, afflicts patients through the progressive degeneration of dopaminergic neurons and sustained neuroinflammation. This study investigates the role of olfactory mucosa\u2010derived mesenchymal stem cell (OM\u2010MSC)\u2010derived exosomes, particularly the long non\u2010coding RNA A2M\u2010AS1 (lncA2M\u2010AS1), in modulating microglial metabolism reprogramming and neuroinflammation in PD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A mouse PD model was established using MPTP injections. Animals received treatments including OM\u2010MSC\u2010derived exosomes knockdown for lncA2M\u2010AS1 or AAV\u2010mediated lncA2M\u2010AS1 overexpression. Motor function was assessed using the open field test and the apomorphine\u2010induced rotation test. Glycolytic metabolism was evaluated by measuring ECAR and OCR using Seahorse XFp Analyzer, and the expression of glycolytic proteins (GLUT1, HK2, PKM2, LDHA) via Western blot. Molecular analyses included qPCR, Western blot, Co\u2010IP, and ubiquitination assays that were performed to investigate the lncA2M\u2010AS1\/CFL1\/ROCK1 regulatory axis. Histological examinations involved immunohistochemistry for TH and IBA1. The expressions of lncA2M\u2010AS1 and ROCK1 were determined in serum obtained from individuals with PD and matched controls.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>LncA2M\u2010AS1 is downregulated in PD patient serum and MPTP mice. OM\u2010MSC exosomal lncA2M\u2010AS1 suppressed microglial glycolysis, reduced pro\u2010inflammatory cytokine release, enhanced neuronal viability, and improved motor function in PD mice. Mechanistically, lncA2M\u2010AS1 directly binds to CFL1 mRNA, promoting ubiquitin\u2010mediated degradation of ROCK1 and inhibiting the CFL1\/ROCK1 pathway. Knockdown of CFL1 or overexpression of lncA2M\u2010AS1 attenuated microglial activation and neuroinflammation, whereas ROCK1 overexpression reversed these protective effects.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>OM\u2010MSC exosomal lncA2M\u2010AS1 ameliorates PD pathogenesis by targeting the CFL1\/ROCK1 axis to reprogram microglial glucose metabolism and suppress neuroinflammation, offering a novel therapeutic strategy for PD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cns.71019","type":"journal-article","created":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T15:35:36Z","timestamp":1783697736000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Olfactory Mucosal Mesenchymal Stem Cell\u2010Derived Exosomal\n                    <scp>LncA2M<\/scp>\n                    \u2010\n                    <scp>AS1<\/scp>\n                    Ameliorates Parkinson's Disease by Regulating Microglial Glucose Metabolic Reprogramming and Neuroinflammation via the\n                    <scp>CFL1<\/scp>\n                    \/\n                    <scp>ROCK1<\/scp>\n                    Axis"],"prefix":"10.1002","volume":"32","author":[{"given":"Jiangshan","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Neurology Central South University Xiangya School of Medicine Affiliated Haikou Hospital  Haikou Hainan Province P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoshuai","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Neurology Central South University Xiangya School of Medicine Affiliated Haikou Hospital  Haikou Hainan Province P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanhui","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Neurology Central South University Xiangya School of Medicine Affiliated Haikou Hospital  Haikou Hainan Province P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Hou","sequence":"additional","affiliation":[{"name":"Department of Neurology Central South University Xiangya School of Medicine Affiliated Haikou Hospital  Haikou Hainan Province P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuang","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Central South University Xiangya School of Medicine Affiliated Haikou Hospital  Haikou Hainan Province P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yujie","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Neurology Central South University Xiangya School of Medicine Affiliated Haikou Hospital  Haikou Hainan Province P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1740-0436","authenticated-orcid":false,"given":"Ying","family":"Xia","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Central South University Xiangya School of Medicine Affiliated Haikou Hospital  Haikou Hainan Province P. R. 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