期刊
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
卷 70, 期 32, 页码 10011-10021出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.jafc.2c03411
关键词
methylglyoxal; Alzheimer's disease; reactive oxygen species; amyloid beta; autophagy
资金
- National Taiwan University Higher Education Sprout Project [NTU-CC-110L893104, NTU-CC-111L892504]
This study using a nematode model found that dietary exposure to MG may exacerbate AD pathology, as high levels of MG exposure led to decreased locomotive behaviors, increased A beta protein accumulation, impaired 5-HT reuptake, increased oxidative stress, and disrupted autophagy pathway. Treatment with the citrus flavonoid nobiletin reduced MG-induced toxicity.
Methylglyoxal (MG) is a precursor of advanced glycation end products usually generated during cooking. The high level of MG in the brain is correlated to the pathogenesis of Alzheimer's disease (AD). However, it is not clear if MG consumed through the diet can cause AD-related toxicity. Herein, the Caenorhabditis elegans (C. elegans) AD model was used to investigate the neurotoxicity after long-term MG exposure at dietary levels. The results showed that C. elegans locomotive behaviors were significantly decreased after 0.1, 0.5, and 1 mM MG exposure (p < 0.001). In amyloid beta (A beta)-expressing transgenic C. elegans strains, 0.5 mM MG significantly promoted A beta accumulation by around 50% in day-8 CL2006 (p < 0.001), enhanced paralysis in CL4176 (p < 0.001) and CL2006 (p < 0.01), and made CL2355 around 17% more vulnerable to 5-HT, indicating impaired serotonin reuptake (p < 0.05). Additionally, 0.5 mM MG significantly increased the reactive oxygen species level (p < 0.001) by inhibiting the expression of stress-response genes including sod-3, gst-4, and hsp-16.2 in day-8 aged worms. Moreover, the autophagic pathway was disrupted through lgg-1, vps-34, and bec-1 expression after MG exposure and A beta accumulation. Treatment with the citrus flavonoid nobiletin reduced the MG-induced toxicity (p < 0.001). Overall, these findings imply that it is possible to exacerbate AD pathogenesis by MG exposure through the diet.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据