{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T10:39:34Z","timestamp":1777718374160,"version":"3.51.4"},"reference-count":25,"publisher":"SAGE Publications","issue":"1","license":[{"start":{"date-parts":[[2025,9,13]],"date-time":"2025-09-13T00:00:00Z","timestamp":1757721600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"name":"MetaCen Therapeutics"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Int J Toxicol"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:p>\n                    Parkinson\u2019s disease (PD) is characterized by the abnormal aggregation of \u03b1-synuclein, which can originate in the gut and propagate to the brain. Recent evidence suggests a correlation between metabolic disorders, particularly diabetes, and PD pathogenesis through the gut\u2013brain axis. Methylglyoxal (MGO), a glucose-derived metabolite produced by gut bacteria such as\n                    <jats:italic toggle=\"yes\">Proteus mirabilis<\/jats:italic>\n                    , is implicated in protein misfolding and glycation. This study investigated whether MGO induced \u03b1-synuclein aggregation in intestinal enteroendocrine cells and explored the underlying mechanisms. Mouse enteroendocrine STC-1 cells were treated with MGO (0.01-1\u00a0mM) for 36\u00a0h, and changes in \u03b1-synuclein aggregation, neuronal markers, and relevant signaling pathways were assessed. MGO at 1\u00a0mM significantly reduced cell viability and neuronal marker expression, and concentrations of 0.1 and 1\u00a0mM increased \u03b1-synuclein aggregation. MGO also inhibited SIRT1 expression, leading to increased Hif-1\u03b1 transcription and reduced expression of autophagy-related proteins Beclin1 and LC3B. These changes were accompanied by mitochondrial dysfunction, as evidenced by decreased Bcl2, increased cytochrome C expression, and reduced levels of the antioxidant factor HO-1. Our findings provide the first evidence that MGO directly induces \u03b1-synuclein aggregation in enteroendocrine cells via the SIRT1-Hif-1\u03b1-autophagy pathway dysregulation, establishing a potential mechanistic link between gut microbiome\u2013derived metabolites and PD pathogenesis. These results suggest that intestinal glycation may be a critical target for preventing \u03b1-synuclein pathology originating in the gut.\n                  <\/jats:p>","DOI":"10.1177\/10915818251378724","type":"journal-article","created":{"date-parts":[[2025,9,13]],"date-time":"2025-09-13T14:09:22Z","timestamp":1757772562000},"page":"22-28","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Methylglyoxal Aggregates \u03b1-Synuclein by Inhibiting SIRT1-Hif-1\u03b1 in Intestinal Enteroendocrine Cells"],"prefix":"10.1177","volume":"45","author":[{"given":"Eugene","family":"Huh","sequence":"first","affiliation":[{"name":"Kyung Hee University"},{"name":"Gachon University"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jin Myeong","family":"Kim","sequence":"additional","affiliation":[{"name":"Gachon University"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seong Hye","family":"Kim","sequence":"additional","affiliation":[{"name":"Gachon University"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yujin","family":"Choi","sequence":"additional","affiliation":[{"name":"Kyung Hee University"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Myoung Gyu","family":"Park","sequence":"additional","affiliation":[{"name":"MetaCen Therapeutics Inc. 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