Role of the Glyoxalase System in Alzheimer’s Disease

Jiang, Lianying; Wang, Jiafeng; Wang, Zhigang; Huang, Wenhui; Yang, Yixia; Cai, Zhiyou; Li, Keshen

doi:10.3233/jad-180413

Cited by 10 publications

(4 citation statements)

References 104 publications

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“…As oxidative stress can facilitate accumulation and function of AGEs and therefore contribute to progression of neuron loss and diabetic encephalopathy (47)(48)(49), whether KWG could reduce AGE-induced ROS production was investigated. Additionally, levels of SOD, GPX and MDA were assessed and the results indicated that KWG increased the expression of SOD, GPX and reduced the secretion of MDA following AGE administration.…”

Section: Discussionmentioning

confidence: 99%

Kuwanon G protects HT22 cells from advanced glycation end product-induced damage

et al. 2021

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The incidence of diabetic encephalopathy is increasing as the population ages. Evidence suggests that formation and accumulation of advanced glycation end products (AGEs) plays a pivotal role in disease progression, but limited research has been carried out in this area. A previous study demonstrated that Kuwanon G (KWG) had significant anti-oxidative stress and anti-inflammatory properties. As AGEs are oxidative products and inflammation is involved in their generation it is hypothesized that KWG may have effects against AGE-induced neuronal damage. In the present study, mouse hippocampal neuronal cell line HT22 was used. KWG was shown to significantly inhibit AGE-induced cell apoptosis in comparison with a control treatment, as determined by both MTT and flow cytometry. Compared with the AGEs group, expression of pro-apoptotic protein Bax was reduced and expression of anti-apoptotic protein Bcl-2 was increased in the AGEs + KWG group. Both intracellular and extracellular levels of acetylcholine and choline acetyltransferase were significantly elevated after KWG administration in comparison with controls whilethe level of acetylcholinesterase decreased. These changes in protein expression were accompanied by increased levels of superoxide dismutase and glutathione peroxidase synthesis and reduced production of malondialdehyde and reactive oxygen species. Intracellular signaling pathway protein levels were determined by western blot and immunocytochemistry. KWG administration was found to prevent AGE-induced changes to the phosphorylation levels of Akt, IκB-α, glycogen synthase kinase 3 (GSK3)-α and β, p38 MAPK and NF-κB p65 suggesting a potential neuroprotective effect of KWG against AGE-induced damage was via the PI3K/Akt/GSK3αβ signaling pathway. The findings of the present study suggest that KWG may be a potential treatment for diabetic encephalopathy.

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Section: Discussionmentioning

confidence: 99%

Kuwanon G protects HT22 cells from advanced glycation end product-induced damage

et al. 2021

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“…Glyoxalases 1 and 2 are enzymes involved in D-lactate conversion respective production in humans as well [37,38]. Just as the system of glyoxalases makes a link between D-lactate and methylglyoxal, the methylglyoxal is further involved in forming advanced glycation end products, and in a wider look, it has a role in oxidative stress neurodegenerative disorders [39][40][41][42]. Enzymes involved in the lactate metabolism are summarized in Table 1.…”

Section: Basic Biochemical Pathways For D-lactic Acidmentioning

confidence: 99%

D-Lactic Acid as a Metabolite: Toxicology, Diagnosis, and Detection

Pohanka

2020

BioMed Research International

117

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Two enantiomers of lactic acid exist. While L-lactic acid is a common compound of human metabolism, D-lactic acid is produced by some strains of microorganism or by some less relevant metabolic pathways. While L-lactic acid is an endogenous compound, D-lactic acid is a harmful enantiomer. Exposure to D-lactic acid can happen by various ways including contaminated food and beverages and by microbiota during some pathological states like short bowel syndrome. The exposure to D-lactic acid cannot be diagnosed because the common analytical methods are not suitable for distinguishing between the two enantiomers. In this review, pathways for D-lactic acid, pathological processes, and diagnostical and analytical methods are introduced followed by figures and tables. The current literature is summarized and discussed.

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“…Aging is an important social problem facing all countries in the world today. One of the neurodegenerative diseases highly related to aging is Alzheimer’s disease (AD), whose incidence increases with age [ 1 , 2 ]. The main clinical manifestations of AD are cognitive and memory impairment, accompanied by atrophy in hippocampus and other related brain areas [ 3 – 6 ] Its recognized pathological features mainly include β-amyloid plaques, neurofibrillary tangles and neuronal death [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

Sirt1 protects against hippocampal atrophy and its induced cognitive impairment in middle-aged mice

et al. 2022

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Background Sirtuin 1 (Sirt1) is a recognized longevity gene and has been shown to be associated with aging and its related diseases. Hippocampal volume is considered to be the most sensitive brain imaging phenotype for cognition, but the effect of Sirt1 on hippocampal morphology during aging has not been reported. Results Herein, we investigated the effect of conditional Sirt1 knockdown on hippocampal volume in middle-aged mice, as well as its cognitive function and the underlying molecular mechanisms. Brain structural magnetic resonance imaging (MRI) showed that adeno-associated virus (AAV) mediated hippocampal Sirt1 knockdown caused hippocampal atrophy in 8-month-old mice. Open field test (OFT) and Morris Water Maze (MWM) test revealed that hippocampal Sirt1 knockdown significantly weakened spatial learning and memory of mice without effect on anxiety and exploratory behavior. Western blotting analysis showed that P-tau levels at serine 396 epitope were significantly increased with slightly decreased T-tau levels, while PSD95 and NMDAR2B levels were obviously reduced, indicating that hippocampal Sirt1 knockdown could activate tau hyperphosphorylation and synaptic damage. Conclusions This work revealed that Sirt1 is an important protective gene against hippocampal atrophy and its induced cognitive impairment during aging, providing potential therapeutic targets for the prevention and intervention of aging-related neuropsychic diseases.

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Role of the Glyoxalase System in Alzheimer’s Disease

Cited by 10 publications

References 104 publications

Kuwanon G protects HT22 cells from advanced glycation end product-induced damage

Kuwanon G protects HT22 cells from advanced glycation end product-induced damage

D-Lactic Acid as a Metabolite: Toxicology, Diagnosis, and Detection

Sirt1 protects against hippocampal atrophy and its induced cognitive impairment in middle-aged mice

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