Inhibitors of Advanced Glycation End Product (AGE) Formation and Accumulation

Sourris, Karly C.; Watson, Anna; Jandeleit-Dahm, Karin

doi:10.1007/164_2020_391

Cited by 41 publications

(26 citation statements)

References 211 publications

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“…They are roughly identified as inflammatory type receptor and clearance receptors with RAGE and OST48 as the most representatives, respectively. [32] In our study, we found that dAGEs decreased OST48 level in female mice while trehalose elevated OST48 in both sexes, but dAGEs or trehalose per se had no effect on RAGE, implicating that the effects induced by dAGEs might be independent from RAGE. This hypothesis was also supported by in vitro study, because we found no tau phosphorylation related key proteins were changed after the extra-addition of FPS-ZM1, a specific high-affinity inhibitor of RAGE.…”

Section: Discussionmentioning

confidence: 41%

“…[34] Our study was the very first to demonstrated that the effect of dietary AGEs on tau phosphorylation might be independent from RAGE. However, it should be mentioned that besides RAGE and OST48, there are many other AGE-binding receptors including AGE-R2, AGER3, and CD36, etc., [32] it is also likely that dietary AGEs might exert its effects on AD pathology via these unmeasured receptors.…”

Section: Discussionmentioning

confidence: 99%

“…RAGE and OST48 are two common receptors for AGEs. [32] Because a sex-specific effect of dAGEs on cognitive function was observed, we also measured ER𝛼 and ER𝛽 protein expression to explore the potential mechanisms. For female mice, in the hippocampus, reduction in OST48 protein expression was observed post dAGEs intervention, while trehalose treatment significantly elevated OST48, ER𝛼 was also significantly elevated post trehalose treatment (Figure 4A).…”

Section: Rage Ost48 Er𝜶 and Er𝜷 Protein Expressionmentioning

confidence: 99%

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Sex‐Specific Neurotoxicity of Dietary Advanced Glycation End Products in APP/PS1 Mice and Protective Roles of Trehalose by Inhibiting Tau Phosphorylation via GSK‐3β‐TFEB

Zhou

Luo

Zhai

et al. 2021

Molecular Nutrition Food Res

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ScopeIt remains unclear whether dietary advanced glycation end products (dAGEs)‐induced cognitive impairment is sex‐dependent. Trehalose may antagonize dAGEs‐induced neurotoxicity via glycogen synthase kinase‐3 beta (GSK3β)‐transcription factor EB (TFEB) signaling.Methods and ResultsThe sex‐specific neurotoxicity of dAGEs and the protective role of trehalose are investigated both in vivo and in vitro. Both sexes of APP/PS1 mice are divided into three groups: that is, control, dAGEs, and dAGEs supplemented with trehalose. SHSY‐5Y cells incubated with AGE‐BSA and trehalose are also utilized. Dietary AGEs impair cognitive function only in female mice, which is restored by trehalose. Trehalose upregulates phosphorylated‐GSK3β serine9 (p‐GSK3β ser9), TFEB and transient receptor potential mucolipin 1, ADAM10, oligosaccharyl transferase‐48, estrogen receptor α and induces TFEB nuclear translocation in hippocampus, elevates IDE and ERβ in cortex, while reduces p‐tau ser396&404, CDK5, cathepsin B, and glial fibrillary acidic protein in hippocampus. Trehalose elevates p‐GSK3β ser9, induces TFEB nuclear translocation, consequently reverses AGE‐BSA‐induced tau phosphorylation in vitro.ConclusionsFemale mice are more susceptible to the deleterious effects of dAGEs on cognitive function, which may be owing to its regulation on ERβ. Trehalose can strongly reverse dAGEs‐induced tau phosphorylation by potentiating TFEB nuclear translocation via inhibiting GSK‐3β.

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Section: Discussionmentioning

confidence: 41%

Section: Discussionmentioning

confidence: 99%

Section: Rage Ost48 Er𝜶 and Er𝜷 Protein Expressionmentioning

confidence: 99%

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Sex‐Specific Neurotoxicity of Dietary Advanced Glycation End Products in APP/PS1 Mice and Protective Roles of Trehalose by Inhibiting Tau Phosphorylation via GSK‐3β‐TFEB

Zhou

Luo

Zhai

et al. 2021

Molecular Nutrition Food Res

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“…Development of destiffening medicines, which could directly prevent AGE cross-linking or break existing cross-links in the arterial wall, is an area of active research and has a great clinical potential. Currently investigated direct AGE inhibitors include pyridoxamine and epalrestat [ 207 ].…”

Section: ‘Arteriometabolomics’ Approachmentioning

confidence: 99%

“…While some progress has already been made in determining therapeutic targets for AS, metabolomics research could further contribute to this endeavor. As reviewed above, the current more intriguing candidate metabolic modulators to improve AS include L-carnitine [ 64 ] and Tau [ 195 ] supplements, TMA-lyase inhibitors [ 72 ], PPARβ/δ activators [ 95 ], Tyr hydroxylase inhibitors [ 163 ], ceramide synthase inhibitors [ 141 ], SMS2 inhibitors [ 141 ], and direct AGE inhibitors [ 207 ].…”

Section: ‘Arteriometabolomics’ Approachmentioning

confidence: 99%

Metabolomics of Arterial Stiffness

Paapstel

Kals

2022

Metabolites

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Arterial stiffness (AS) is one of the earliest detectable signs of structural and functional alterations of the vessel wall and an independent predictor of cardiovascular events and death. The emerging field of metabolomics can be utilized to detect a wide spectrum of intermediates and products of metabolism in body fluids that can be involved in the pathogenesis of AS. Research over the past decade has reinforced this idea by linking AS to circulating acylcarnitines, glycerophospholipids, sphingolipids, and amino acids, among other metabolite species. Some of these metabolites influence AS through traditional cardiovascular risk factors (e.g., high blood pressure, high blood cholesterol, diabetes, smoking), while others seem to act independently through both known and unknown pathophysiological mechanisms. We propose the term ‘arteriometabolomics’ to indicate the research that applies metabolomics methods to study AS. The ‘arteriometabolomics’ approach has the potential to allow more personalized cardiovascular risk stratification, disease monitoring, and treatment selection. One of its major goals is to uncover the causal metabolic pathways of AS. Such pathways could represent valuable treatment targets in vascular ageing.

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Peperomia pellucida (L.) Kunth suppresses glycation‐induced inflammatory response in human retinal pigment epithelial cell line ARPE‐19 via JAK‐STAT3 signaling

Ho,

Yong,

Lim

et al. 2024

Archiv der Pharmazie

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The formation of advanced glycation end product (AGE) is a risk factor for diabetic retinopathy. Since the current treatment for diabetic retinopathy is accompanied by side effects, preliminary findings have suggested Peperomia pellucida (L.) Kunth as a potential alternative therapeutic option for diabetic retinopathy. This study aimed to elucidate the anti‐inflammatory mechanism of P. pellucida in the AGE‐stimulated human retinal pigment epithelial cell line ARPE‐19. Phytochemical analysis revealed phenylpronanoids, terpenes, and fatty acids in P. pellucida. Through in vitro cell viability assay, the P. pellucida methanolic extract (IC50 = 8.70 mg/mL) and ethyl acetate fraction (IC50 = 7.34 mg/mL) were considered as non toxic for ARPE‐19. AGE induced an inflammatory response in ARPE‐19 by upregulating the gene (2.4–5.8‐fold) and protein (1.4–2.3‐fold) expression of signal transducer and activator of transcription 3 (STAT3), interleukin‐8 (IL‐8), monocyte chemoattractant protein‐1, matrix metalloproteinase 2, and vascular endothelial growth factor. At 1.5 mg/mL, P. pellucida methanolic extract suppressed IL‐8 expression (p < 0.05), implying its anti‐inflammatory action at the early inflammatory stage through the Janus kinase (JAK)‐STAT3 pathway. The methanolic extract also restored the ARPE‐19 viability under AGE‐induced inflammatory stress. The downregulation of inflammatory biomarkers along the JAK‐STAT3 pathway suggested P. pellucida as a promising anti‐inflammatory source for diabetic retinopathy.

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Inhibitors of Advanced Glycation End Product (AGE) Formation and Accumulation

Cited by 41 publications

References 211 publications

Sex‐Specific Neurotoxicity of Dietary Advanced Glycation End Products in APP/PS1 Mice and Protective Roles of Trehalose by Inhibiting Tau Phosphorylation via GSK‐3β‐TFEB

Sex‐Specific Neurotoxicity of Dietary Advanced Glycation End Products in APP/PS1 Mice and Protective Roles of Trehalose by Inhibiting Tau Phosphorylation via GSK‐3β‐TFEB

Metabolomics of Arterial Stiffness

Peperomia pellucida (L.) Kunth suppresses glycation‐induced inflammatory response in human retinal pigment epithelial cell line ARPE‐19 via JAK‐STAT3 signaling

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