{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T13:51:30Z","timestamp":1790949090419,"version":"4.1.0"},"reference-count":51,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2026,1,4]],"date-time":"2026-01-04T00:00:00Z","timestamp":1767484800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Science and Technology Council","award":["110-2637-B-020-007"],"award-info":[{"award-number":["110-2637-B-020-007"]}]},{"name":"National Science and Technology Council","award":["111-2622-B-020-003"],"award-info":[{"award-number":["111-2622-B-020-003"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Methylglyoxal (MG), a reactive dicarbonyl metabolite associated with diabetes and metabolic disorders, contributes to carbonyl stress, neuroinflammation, and Alzheimer-like neurodegeneration. This study investigated the neuroprotective effects of propyl gallate (PG), a phenolic antioxidant widely used as a food additive, against MG-induced cognitive impairment in mice. Male C57BL\/6J mice were exposed to 1% MG in drinking water for eight weeks and orally administered PG (20, 40, or 100 mg\/kg\/d). Behavioral tests demonstrated that PG significantly improved spatial learning and recognition memory and alleviated anxiety-like behavior induced by MG. Histological and biochemical analyses revealed that PG reduced hippocampal neuronal damage, suppressed tau hyperphosphorylation and amyloid-\u03b2 (A\u03b2) accumulation, and attenuated the overexpression of pro-inflammatory cytokines TNF-\u03b1 and IL-6. Furthermore, PG increased PI3K expression and Akt phosphorylation while reducing activation of GSK-3\u03b2, counteracting the MG-induced suppression of this pathway and aligning with reduced tau hyperphosphorylation. These findings indicate that PG protects against MG-related cognitive dysfunction through modulation of neuroinflammatory responses and survival-related signaling pathways, highlighting its potential as a neuroprotective dietary antioxidant for metabolic stress-associated neurodegenerative disorders.<\/jats:p>","DOI":"10.3390\/ijms27010511","type":"journal-article","created":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T13:35:47Z","timestamp":1767620147000},"page":"511","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Propyl Gallate Attenuates Methylglyoxal-Induced Alzheimer-like Cognitive Deficits and Neuroinflammation in Mice"],"prefix":"10.3390","volume":"27","author":[{"given":"Hui-Yun","family":"Tsai","sequence":"first","affiliation":[{"name":"Department of Nutrition and Health Science, Fooyin University, Kaohsiung 831301, Taiwan"},{"name":"Aging and Disease Prevention Research Center, Fooyin University, Kaohsiung 831301, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Qiu","sequence":"additional","affiliation":[{"name":"Department of Food Science, National Pingtung University of Science and Technology, Pingtung 912301, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han-Wei","family":"Liao","sequence":"additional","affiliation":[{"name":"Department of Food Science, National Pingtung University of Science and Technology, Pingtung 912301, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chi-I","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Biological Science and Technology, National Pingtung University of Science and Technology, Pingtung 912301, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Hsiang","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Medical & Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN 46202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8273-2085","authenticated-orcid":false,"given":"Chi-Tang","family":"Ho","sequence":"additional","affiliation":[{"name":"Department of Food Science, Rutgers, The State University of New Jersey, New Brunswick, NJ 08901, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8031-8312","authenticated-orcid":false,"given":"Yu-Kuo","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Food Science, National Pingtung University of Science and Technology, Pingtung 912301, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"115522","DOI":"10.1016\/j.bcp.2023.115522","article-title":"Alzheimer\u2019s disease: Insights and new prospects in disease pathophysiology, biomarkers and disease-modifying drugs","volume":"211","author":"Monteiro","year":"2023","journal-title":"Biochem. 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