{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T16:37:51Z","timestamp":1790786271632,"version":"4.1.0"},"reference-count":164,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2024,2,17]],"date-time":"2024-02-17T00:00:00Z","timestamp":1708128000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Graduate Studies and Scientific Research at the University of Bisha"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>This comprehensive exploration delves into the intricate interplay of methylglyoxal (MG) and glyoxalase 1 (GLO I) in various physiological and pathological contexts. The linchpin of the narrative revolves around the role of these small molecules in age-related issues, diabetes, obesity, cardiovascular diseases, and neurodegenerative disorders. Methylglyoxal, a reactive dicarbonyl metabolite, takes center stage, becoming a principal player in the development of AGEs and contributing to cell and tissue dysfunction. The dual facets of GLO I\u2014activation and inhibition\u2014unfold as potential therapeutic avenues. Activators, spanning synthetic drugs like candesartan to natural compounds like polyphenols and isothiocyanates, aim to restore GLO I function. These molecular enhancers showcase promising outcomes in conditions such as diabetic retinopathy, kidney disease, and beyond. On the contrary, GLO I inhibitors emerge as crucial players in cancer treatment, offering new possibilities in diseases associated with inflammation and multidrug resistance. The symphony of small molecules, from GLO I activators to inhibitors, presents a nuanced understanding of MG regulation. From natural compounds to synthetic drugs, each element contributes to a molecular orchestra, promising novel interventions and personalized approaches in the pursuit of health and wellbeing. The abstract concludes with an emphasis on the necessity of rigorous clinical trials to validate these findings and acknowledges the importance of individual variability in the complex landscape of health.<\/jats:p>","DOI":"10.3390\/life14020263","type":"journal-article","created":{"date-parts":[[2024,2,19]],"date-time":"2024-02-19T10:40:15Z","timestamp":1708339215000},"page":"263","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Molecular Assessment of Methylglyoxal-Induced Toxicity and Therapeutic Approaches in Various Diseases: Exploring the Interplay with the Glyoxalase System"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0733-3417","authenticated-orcid":false,"given":"Muhanad","family":"Alhujaily","sequence":"first","affiliation":[{"name":"Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, University of Bisha, Bisha 61922, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,2,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2112","DOI":"10.1002\/mc.22668","article-title":"Glyoxalase 2 drives tumorigenesis in human prostate cells in a mechanism involving androgen receptor and p53-p21 axis","volume":"56","author":"Antognelli","year":"2017","journal-title":"Mol. 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