TAGE (toxic AGEs) hypothesis in various chronic diseases
Abstract
The advanced stage of the glycation process (one of the post-translational modifications of proteins) leads to the formation of advanced glycation end-products (AGEs) and plays an important role in the pathogenesis of angiopathy in diabetic patients, in aging, and in neurodegenerative diseases. However, it is still not clear which AGEs subtypes play a pathogenetic role and which of several AGEs receptor mediate AGEs effects on cells. We have provided direct immunochemical evidence for the existence of six distinct AGEs structures (AGEs-1 to -6) within the AGEs-modified proteins and peptides that circulate in the serum of diabetic patients. Recently we demonstrated for the first time that glyceraldehyde-derived AGEs (AGEs-2) and glycolaldehyde-derived AGEs (AGE-3) have diverse biological activities on vascular wall cells, mesangial cells, Schwann cells, malignant melanoma cells and cortical neurons. We also demonstrated for the first time that acetaldehyde (AA)-derived AGEs (AA-AGE) have cytotoxic activity on cortical neurons and the AA-AGE epitope was detected in human brain of alcoholics. These results indicate that of the various types of AGEs structures that can form in vivo, the toxic AGEs (TAGE) structures (AGEs 2, 3, and AA-AGE), but not non-toxic AGEs (N-carboxymethyllysine, pentosidine, pyrraline etc.) are likely to play an important role in the pathophysiological processes associated with AGEs formation.
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“The second group includes AGE-1 (glucose-derived AGEs), AGE-2 (glyceraldehyde-derived AGEs), AGE-3 (glycolaldehyde-derived AGEs), AGE-4 (GO/glyoxal, MGO/methylglyoxalderived AGEs), AGE-5 (glyoxal-derived AGEs), AGE-6 (3-deoxyglucosone-derived AGEs) and acetaldehyde-derived AGEs (AA-AGEs) [191].”
Background
- Authors
- Takeuchi, M., & Yamagishi, S.
- Affiliations
- Hokuriku University (JP)
- Kurume University (JP)
- Corresponding author
- Takeuchi, M
- Venue
- Medical Hypotheses
- Publisher
- Elsevier BV
- Published
- 2004
- Volume
- 63
- Issue
- 3
- Pages
- 449-452
- ISSN
- 0306-9877 (ISSN-L)
- OpenAlex
- W2043932921
- Cited by
- 116
- References
- 20
- Citations by year
- 2025: 3 · 2024: 6 · 2023: 8 · 2022: 6 · 2021: 9 · 2020: 7 · 2019: 2 · 2018: 1 · 2017: 4 · 2016: 9 · 2015: 10 · 2014: 4 · 2013: 4 · 2012: 4
- FWCI
- 3.81
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Medical Hypotheses (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Yale University
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Advanced Glycation End Products research
- Life Sciences › Agricultural and Biological Sciences › Food Science › Potato Plant Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Glycosylation and Glycoproteins Research
- Keywords
- advanced glycation end products, diabetic vascular disease, neurodegenerative diseases, aging, chronic disease, cortical neurons, Schwann cells, mesangial cells, melanoma cells, alcoholism, pentosidine, pyrraline
- MeSH terms
- Aging, Alcoholism, Aldehydes, Animals, Chronic Disease, Clinical Trials as Topic, Diabetic Angiopathies, Glyceraldehyde, Humans, Models, Biological, Biomarkers, Glycation End Products, Advanced, Neurodegenerative Diseases
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