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Neurotoxicity of methylglyoxal and 3‐deoxyglucosone on cultured cortical neurons: Synergism between glycation and oxidative stress, possibly involved in neurodegenerative diseases
Author(s) -
Kikuchi Seiji,
Shinpo Kazuyoshi,
Moriwaka Fumio,
Makita Zenji,
Miyata Toshio,
Tashiro Kunio
Publication year - 1999
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/(sici)1097-4547(19990715)57:2<280::aid-jnr14>3.0.co;2-u
Subject(s) - glycation , methylglyoxal , oxidative stress , neurotoxicity , neurodegeneration , neuroprotection , chemistry , reactive oxygen species , pharmacology , biochemistry , medicine , toxicity , receptor , enzyme , disease , organic chemistry
In this study, we investigate the neurotoxicity of glycation, particularly early‐stage glycation, and its mechanisms, which are possibly synergized with oxidative stress. Methylglyoxal (MG) and 3‐deoxyglucosone (3DG), intermediate products of glycation, are known to further accelerate glycation and advanced glycation endproducts (AGEs) formation. Both compounds showed neurotoxicity on cultured cortical neurons and these effects were associated with reactive oxygen species production followed by neuronal apoptosis. Pretreatment with N‐acetylcysteine induced neuroprotection against MG and 3DG. Cotreatment, but not pretreatment, with aminoguanidine protected neurons against the neurotoxicities of both compounds. The present study provides the first evidence that MG and 3DG are neurotoxic to cortical neurons in culture. Interference with the process by which glycation and AGEs formation occur may provide new therapeutic opportunities to reduce the pathophysiological changes associated with neurodegeneration, if, as indicated here, the participation of glycoxidation in the pathogenesis of neurodegenerative diseases is essential. J. Neurosci. Res. 57:280–289, 1999. © 1999 Wiley‐Liss, Inc.