Advanced glycation end products as biomarkers and gerontotoxins – A basis to explore methylglyoxal-lowering agents for Alzheimer’s disease?

Krautwald, Martina; Münch, Gerald

doi:10.1016/j.exger.2010.03.001

Cited by 93 publications

(59 citation statements)

References 74 publications

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“…AGEs modification may explain many of the neuropathological and biochemical features of AD such as extensive protein cross‐linking, oxidative stress, and neuronal cell death. In vivo studies found that AGEs are co‐localized with protein deposits such as Aβ plaques in AD (Choei et al ., 2004; Krautwald & Munch, 2010). …”

Section: Discussionmentioning

confidence: 99%

High dietary advanced glycation end products are associated with poorer spatial learning and accelerated Aβ deposition in an Alzheimer mouse model

et al. 2016

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SummaryThere is growing evidence of the involvement of advanced glycation end products (AGEs) in the pathogenesis of neurodegenerative processes including Alzheimer's disease (AD) and their function as a seed for the aggregation of Aβ, a hallmark feature of AD. AGEs are formed endogenously and exogenously during heating and irradiation of foods. We here examined the effect of a diet high in AGEs in the context of an irradiated diet on memory, insoluble Aβ42, AGEs levels in hippocampus, on expression of the receptor for AGEs (RAGE), and on oxidative stress in the vasculature. We found that AD‐like model mice on high‐AGE diet due to irradiation had significantly poorer memory, higher hippocampal levels of insoluble Aβ42 and AGEs as well as higher levels of oxidative stress on vascular walls, compared to littermates fed an isocaloric diet. These differences were not due to weight gain. The data were further supported by the overexpression of RAGE, which binds to Aβ42 and regulates its transport across the blood–brain barrier, suggesting a mediating pathway. Because exposure to AGEs can be diminished, these insights provide an important simple noninvasive potential therapeutic strategy for alleviating a major lifestyle‐linked disease epidemic.

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Section: Discussionmentioning

confidence: 99%

High dietary advanced glycation end products are associated with poorer spatial learning and accelerated Aβ deposition in an Alzheimer mouse model

et al. 2016

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“…Another approach to the inhibition of tangle formation might be the inhibition of tau crosslinking e.g. by advanced glycation endproducts by the use of anti-glycation agents (Kuhla et al 2007;Krautwald et al 2010;. Furthermore, it has been suggested that microtubule ( However, with growing uncertainty of the therapeutic potential of drugs targeting amyloid and tau, other novel therapies have recently been proposed, including those targeting glycation, oxidative stress and inflammation ).…”

Section: Anti-tangle Drugsmentioning

confidence: 99%

Induced pluripotent stem cells as tools for disease modelling and drug discovery in Alzheimer’s disease

et al. 2012

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The use of induced pluripotent stem cells (iPSCs), whereby a patient's somatic cells can be reprogrammed to a pluripotent state by the forced expression of a defined set of transcription factors, has the potential to enable in vitro disease modelling and be used for drug discovery programs. Alzheimer's disease (AD) is a progressive neurodegenerative brain disorder that leads to a decline in memory and cognition. Fibroblasts were taken from AD patients (or non‐AD controls) and cultured under specific conditions to generate iPSCs which were then provided with growth factors to allow differentiation into neurons. While AD‐iPSCs were morphologically indistinguishable from control‐iPSCs, differentiated cells showed differing responses to both cellular stresses and neuroprotective drugs. Since these cells are derived from individual patients, the use of iPSCs has provided novel insights into disease pathogenesis, providing information on an individual's variations in the disease process and their cellular response to drugs.

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“…Connections to vascular diseases, diabetic complications and diabetic neuropathy, and amyloid-type neurodegenerative disease, among other areas, are being investigated (13,15,118). In the area of vascular disease and diabetes, a recent study has reported that increased MG derived AGE appear to be associated with an increased risk of cardiovascular events in type 2 diabetic patients (119).…”

Section: Advanced Glycation End-products (Age) and The Dicarbonyl Promentioning

confidence: 99%

Glyoxalase biochemistry

Honek

2015

Biomolecular Concepts

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Abstract:The glyoxalase enzyme system utilizes intracellular thiols such as glutathione to convert α-ketoaldehydes, such as methylglyoxal, into D-hydroxyacids. This overview discusses several main aspects of the glyoxalase system and its likely function in the cell. The control of methylglyoxal levels in the cell is an important biochemical imperative and high levels have been associated with major medical symptoms that relate to this metabolite's capability to covalently modify proteins, lipids and nucleic acid.

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Advanced glycation end products as biomarkers and gerontotoxins – A basis to explore methylglyoxal-lowering agents for Alzheimer’s disease?

Cited by 93 publications

References 74 publications

High dietary advanced glycation end products are associated with poorer spatial learning and accelerated Aβ deposition in an Alzheimer mouse model

High dietary advanced glycation end products are associated with poorer spatial learning and accelerated Aβ deposition in an Alzheimer mouse model

Induced pluripotent stem cells as tools for disease modelling and drug discovery in Alzheimer’s disease

Glyoxalase biochemistry

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