Advanced glycation end products enhance amyloid precursor protein expression by inducing reactive oxygen species

Ko, Shun‐Yao; Lin, Yea-Pyng; Lin, Yi-Shiuan; Chang, Shu‐Shing

doi:10.1016/j.freeradbiomed.2010.05.005

Cited by 82 publications

(63 citation statements)

References 80 publications

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“…Brain deposits of AGEs and Aβ are thought to be age related (13)(14)(15)(16)(27)(28)(29)(30)(31). The current study shows that both of these elements were increased in brains of old MG + mice to levels similar to those in old Reg controls.…”

Section: Discussionsupporting

confidence: 58%

“…Nonetheless, the prominent gliosis noted in the hippocampus of the MG + mice, coupled with suppressed SIRT1 and AGER1, is consistent with an MG-mediated inflammatory response. The AGE aggregates observed in these mice could have elicited inflammatory responses (27)(28)(29)(30), partly via RAGE activation (14,35). Whether the effects in MG + mice are a reflection of altered blood-brain barrier, high intracerebral OS, or both, remains to be established.…”

Section: Discussionmentioning

confidence: 98%

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Oral glycotoxins are a modifiable cause of dementia and the metabolic syndrome in mice and humans

Cai

Uribarri²,

Zhu

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

146

106

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Age-associated dementia and Alzheimer's disease (AD) are currently epidemic. Neither their cause nor connection to the metabolic syndrome (MS) is clear. Suppression of deacetylase survival factor sirtuin 1 (SIRT1), a key host defense, is a central feature of AD. Age-related MS and diabetes are also causally associated with suppressed SIRT1 partly due to oxidant glycotoxins [advanced glycation end products (AGEs)]. Changes in the modern diet include excessive nutrient-bound AGEs, such as neurotoxic methyl-glyoxal derivatives (MG). To determine whether dietary AGEs promote AD, we evaluated WT mice pair-fed three diets throughout life:, and regular (Reg) chow. Older MG + -fed mice, similar to old Reg controls, developed MS, increased brain amyloid-β 42 , deposits of AGEs, gliosis, and cognitive deficits, accompanied by suppressed SIRT1, nicotinamide phosphoribosyltransferase, AGE receptor 1, and PPARγ. These changes were not due to aging or caloric intake, as neither these changes nor the MS were present in age-matched, pair-fed MG − mice. The mouse data were enhanced by significant temporal correlations between high circulating AGEs and impaired cognition, as well as insulin sensitivity in older humans, in whom dietary and serum MG levels strongly and inversely associated with SIRT1 gene expression. The data identify a specific AGE (MG) as a modifiable risk factor for AD and MS, possibly acting via suppressed SIRT1 and other host defenses, to promote chronic oxidant stress and inflammation. Because SIRT1 deficiency in humans is both preventable and reversible by AGE reduction, a therapeutic strategy that includes AGE reduction may offer a new strategy to combat the epidemics of AD and MS.neural | insulin resistance | obesity | nutrition | caloric restriction

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Section: Discussionsupporting

confidence: 58%

Section: Discussionmentioning

confidence: 98%

Oral glycotoxins are a modifiable cause of dementia and the metabolic syndrome in mice and humans

Cai

Uribarri²,

Zhu

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

146

106

View full text Add to dashboard Cite

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“…Moreover, some proteins implied in neurodegenerative diseases can directly undergo the glycation reaction, which promotes their aggregation; this is the case for Aβ, τ protein and α-synuclein as studied post-mortem or in vitro (187)(188)(189) . AGE, when added in vitro in neuroblastoma cells or injected in vivo in mice, could also raise Aβ level by inducing the expression of precursor protein APP (190) . Thus, several deregulations induced by HCIAS also occur in the brain, where they could contribute to age-related alteration of cognitive functions, especially by promoting aggregation of misfolded protein involved in neurodegenerative diseases.…”

Section: Nutrition Research Reviewsmentioning

confidence: 99%

Similarities and interactions between the ageing process and high chronic intake of added sugars

et al. 2017

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In our societies, the proportions of elderly people and of obese individuals are increasing. Both factors are associated with high health-related costs. During obesity, many authors suggest that it is a high chronic intake of added sugars (HCIAS) that triggers the shift towards pathology. However, the majority of studies were performed in young subjects and only a few were interested in the interaction with the ageing process. Our purpose was to discuss the metabolic effects of HCIAS, compare with the effects of ageing, and evaluate how deleterious the combined action of HCIAS and ageing could be. This effect of HCIAS seems mediated by fructose, targeting the liver first, which may lead to all subsequent metabolic alterations. The first basic alterations induced by fructose are increased oxidative stress, protein glycation, inflammation, dyslipidaemia and insulin resistance. These alterations are also present during the ageing process, and are closely related to each other, one leading to the other. These basic alterations are also involved in more complex syndromes, which are also favoured by HCIAS, and present during ageing. These include non-alcoholic fatty liver disease, hypertension, neurodegenerative diseases, sarcopenia and osteoporosis. Cumulative effects of ageing and HCIAS have been seldom tested and may not always be strictly additive. Data also suggest that some of the metabolic alterations that are more prevalent during ageing could be related more with nutritional habits than to intrinsic ageing. In conclusion, it is clear that HCIAS interacts with the ageing process, accelerates the accumulation of metabolic alterations, and that it should be avoided.

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“…More recently, both in vitro and in vivo studies have shown that amyloid precursor protein (APP) expression is upregulated by AGEs, leading to their increased β-amyloid levels. The increase in -amyloid levels could be effectively blocked with the ROS inhibitor, N-acetyl-L-cysteine [44]. Neurofibrillary tangles (NFTs) are most common primary marker of AD.…”

Section: Glycation In Alzheimer's Diseasementioning

confidence: 99%

The role of advanced glycation end products in various types of neurodegenerative disease: a therapeutic approach

Salahuddin

Rabbani

Khan

2014

Cellular and Molecular Biology Letters

148

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of advanced glycation end products; ROS -reactive oxygen species; SNCA -synuclein alpha; sRAGE -soluble receptor of advanced glycation end products; TTR -transthyretin; TKtransketolase; TNF -tumor necrosis factor-α; TPP -thiamine pyrophosphate Review THE ROLE OF ADVANCED GLYCATION END PRODUCTS IN VARIOUS TYPES OF NEURODEGENERATIVE DISEASE:A THERAPEUTIC APPROACH Abstract: Protein glycation is initiated by a nucleophilic addition reaction between the free amino group from a protein, lipid or nucleic acid and the carbonyl group of a reducing sugar. This reaction forms a reversible Schiff base, which rearranges over a period of days to produce ketoamine or Amadori products. The Amadori products undergo dehydration and rearrangements and develop a cross-link between adjacent proteins, giving rise to protein aggregation or advanced glycation end products (AGEs). A number of studies Unauthenticated Download Date | 5/11/18 1:17 PM

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Advanced glycation end products enhance amyloid precursor protein expression by inducing reactive oxygen species

Cited by 82 publications

References 80 publications

Oral glycotoxins are a modifiable cause of dementia and the metabolic syndrome in mice and humans

Oral glycotoxins are a modifiable cause of dementia and the metabolic syndrome in mice and humans

Similarities and interactions between the ageing process and high chronic intake of added sugars

The role of advanced glycation end products in various types of neurodegenerative disease: a therapeutic approach

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