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Chemical research in toxicology v.30 no.1, 2017년, pp.38 - 42   SCI SCIE
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AGEs/RAGE-Related Neurodegeneration: daf-16 as a Mediator, Insulin as an Ameliorant, and C. elegans as an Expedient Research Model

Pinkas, Adi Aschner, Michael
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    Advanced glycation end-products (AGEs) are nonenzymatically glycated proteins, lipids, and nucleic acids. These compounds both originate exogenously and are formed endogenously, and they are associated, along with one of their receptors (RAGE), with a variety of pathologies and neurodegeneration. Some of their deleterious effects include affecting insulin signaling and FOXO-related pathways in both receptor-dependent and -independent manners. A potential ameliorating agent for these effects is insulin, which is being studied in several in vivo and in vitro models; one of these models is C. elegans , whose maintenance, genetic malleability, and well-described longevity-related pathways make it an optimal complementary model for assessing these objectives. In the realm of neuroscience, this model is currently being used only for general assessment of neurodegeneration and shortened lifespan. We suggest that characterization of (a) the effects of AGEs/RAGE on specific neurotransmitter systems, (b) the role of the daf-2/daf-16 pathway in these neurodegenerative processes, and (c) the amending properties of insulin would greatly contribute to a more comprehensive understanding of AGEs-related neurodegeneration and, potentially, would lead to developing efficient therapeutic strategies. Graphic Abstract


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