{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T07:26:05Z","timestamp":1774596365109,"version":"3.50.1"},"reference-count":57,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T00:00:00Z","timestamp":1773705600000},"content-version":"vor","delay-in-days":16,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"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":["Journal of Pineal Research"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Chronic manganese (Mn) exposure induces severe neurotoxicity, characterized by impaired neurogenesis and disrupted metabolic homeostasis. Although melatonin (MT) possesses established neuroprotective properties, its clinical utility is hindered by poor bioavailability and limited brain delivery. Here, we developed a brain\u2010targeted, rabies virus glycoprotein (RVG)\u2010modified liposomal delivery system encapsulating melatonin (MT@RVG\u2010Lip) to enhance therapeutic efficacy. Multi\u2010omics analyses including brain and intestinal transcriptomics, serum metabolomics, and gut metagenomics were conducted to elucidate the underlying mechanisms. MT@RVG\u2010Lip significantly improved motor deficits and enhanced neurogenesis while reducing neuroinflammation in Mn\u2010exposed mice. Compared with regular MT and CaNa\n                    <jats:sub>2<\/jats:sub>\n                    \u2010EDTA, MT@RVG\u2010Lip more effectively alleviated Mn\u2010disrupted gene expression in neurogenesis regions, particularly genes involved in amino acid metabolism. Additionally, MT@RVG\u2010Lip demonstrated a regulatory effect on serum amino acid profiles and intestinal transporter gene expression. Gut microbiota analysis further revealed that MT@RVG\u2010Lip partially reversed Mn\u2010associated dysbiosis and promoted the improvement of key amino acid\u2010related microbiota\u2010mediated metabolic pathways. The RVG\u2010modified liposomal formulation conferred sustained release and improved brain\u2010targeting capability, prolonging MT bioavailability and enhancing therapeutic outcomes. These findings provide a new mechanistic framework for MT\u2010based interventions in neurodegenerative diseases and highlight the therapeutic potential of multifunctional delivery strategies.\n                  <\/jats:p>","DOI":"10.1111\/jpi.70137","type":"journal-article","created":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T13:35:08Z","timestamp":1773754508000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Brain\u2010Targeted RVG\u2010Liposomal Melatonin Ameliorates Manganese Neurotoxicity by Enhancing Neurogenesis and Modulating Systemic Amino Acid Profiles"],"prefix":"10.1111","volume":"78","author":[{"given":"Xueting","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Occupational Health and Environmental Health, School of Public Health Capital Medical University  Beijing China"},{"name":"Beijing Key Laboratory of Environment and Aging, School of Public Health Capital Medical 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