Neurotoxicity of Acetaldehyde-Derived Advanced Glycation End Products for Cultured Cortical Neurons
Abstract
The Maillard reaction that leads to the formation of advanced glycation end products (AGEs) plays an important role in the pathogenesis of angiopathy in diabetic patients, in aging, and in neurodegenerative processes. We hypothesize that acetaldehyde (AA), one of the main metabolites of alcohol, may be involved in alcohol-induced neurotoxicity in vivo by formation of AA-derived AGEs (AA-AGEs) with brain proteins. Incubation of cortical neurons with AA-AGE produced a dose-dependent increase in neuronal cell-death, and the neurotoxicity of AA-AGE was neutralized by the addition of an anti-AA-AGE-specific antibody, but not by anti-N-ethyllysine (NEL) antibody. The AA-AGE epitope was detected in human brain of alcoholism. We propose that the structural epitope AA-AGE is an important toxic moiety for neuronal cells in alcoholism.
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Direct exposure of AA-AGE adducts to cortical neurons triggers ROS generation, leading to oxidative stress and consequently neuronal apoptosis and degeneration in a dose-dependent manner; these effects can be prevented by NAC or anti-AA-AGE antibody, suggesting a direct role for AA-AGE adducts in generating oxidative stress-induced neurotoxicity.
“In neurons, direct exposure of AA-AGE adducts to cortical neurons triggers ROS generation, leading to oxidative stress and consequently neuronal apoptosis and degeneration in a dose-dependent manner.”
From Advanced glycation end products (AGEs) and other adducts in aging-related diseases and alcohol-mediated tissue injury (2021) · cites this paper as [199]
Consumption of anti-inflammatory antioxidants from natural dietary supplements and/or synthetic origins can help reduce the incidence and severity of AGE-associated inflammation and related disorders.
“Furthermore, consumption of anti-inflammatory antioxidants from natural dietary supplements279,281,282,290 and/or synthetic origins199 can help reduce the incidence and severity of AGE-associated inflammation and related disorders.”
From Advanced glycation end products (AGEs) and other adducts in aging-related diseases and alcohol-mediated tissue injury (2021) · cites this paper as [199]
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- Authors
- Takeuchi, M., Watai, T., Sasaki, N., Choei, H., Iwaki, M., Ashizawa, T., Inagaki, Y., Yamagishi, S.-I., Kikuchi, S., Riederer, P., Saito, T., Bucala, R., & Kameda, Y.
- Affiliations
- Kurume University (JP)
- Corresponding author
- Takeuchi, Masayoshi
- Venue
- Journal of Neuropathology & Experimental Neurology
- Publisher
- Oxford University Press (OUP)
- Published
- 2003-05
- Volume
- 62
- Issue
- 5
- Pages
- 486-496
- ISSN
- 0022-3069 (ISSN-L)
- 1554-6578
- OpenAlex
- W24612822
- Cited by
- 36
- References
- 42
- Citations by year
- 2024: 4 · 2023: 2 · 2022: 1 · 2021: 1 · 2019: 2 · 2018: 1 · 2017: 2 · 2015: 4 · 2013: 1
- FWCI
- 1.89
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neuropathology & Experimental Neurology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ministry of Education, Culture, Sports, Science and Technology
- Japan Society for the Promotion of Science
- 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
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- acetaldehyde, advanced glycation end products, neurotoxicity, cortical neurons, neuronal cell death, Maillard reaction, alcoholism, alcohol neurotoxicity, brain proteins
- MeSH terms
- Acetaldehyde, Albumins, Alcoholism, Animals, Antibodies, Cattle, Cells, Cultured, Cerebral Cortex, Humans, Neurons, Rabbits, Glycation End Products, Advanced, Apoptosis, Rats
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