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The Possible Mechanism of Advanced Glycation End Products (AGEs) for Alzheimer’s Disease

Amyloid precursor protein (APP) has been modified by β and γ-secretase that cause amyloid deposits (plaques) in neuronal cells. Glyceraldhyde-derived AGEs has been identified as a major source of neurotoxicity in Alzheimer’s disease (AD). In a previous study, we demonstrated that glyceraldehyde-deri...

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Autores principales: Ko, Shun-Yao, Ko, Hshin-An, Chu, Kuo-Hsiung, Shieh, Tzong-Ming, Chi, Tzong-Cherng, Chen, Hong-I, Chang, Weng-Cheng, Chang, Shu-Shing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4654523/
https://www.ncbi.nlm.nih.gov/pubmed/26587989
http://dx.doi.org/10.1371/journal.pone.0143345
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author Ko, Shun-Yao
Ko, Hshin-An
Chu, Kuo-Hsiung
Shieh, Tzong-Ming
Chi, Tzong-Cherng
Chen, Hong-I
Chang, Weng-Cheng
Chang, Shu-Shing
author_facet Ko, Shun-Yao
Ko, Hshin-An
Chu, Kuo-Hsiung
Shieh, Tzong-Ming
Chi, Tzong-Cherng
Chen, Hong-I
Chang, Weng-Cheng
Chang, Shu-Shing
author_sort Ko, Shun-Yao
collection PubMed
description Amyloid precursor protein (APP) has been modified by β and γ-secretase that cause amyloid deposits (plaques) in neuronal cells. Glyceraldhyde-derived AGEs has been identified as a major source of neurotoxicity in Alzheimer’s disease (AD). In a previous study, we demonstrated that glyceraldehyde-derived AGEs increase APP and Aβ via ROS. Furthermore, the combination of AGEs and Aβ has been shown to enhance neurotoxicity. In mice, APP expression is increased by tail vein injection of AGEs. This evidence suggests a correlation between AGEs and the development of AD. However, the role played by AGEs in the pathogenesis of AD remains unclear. In this report, we demonstrate that AGEs up-regulate APP processing protein (BACE and PS1) and Sirt1 expression via ROS, but do not affect the expression of downstream antioxidant genes HO-1 and NQO-1. Moreover, we found that AGEs increase GRP78 expression and enhance the cell death-related pathway p53, bcl-2/bax ratio, caspase 3. These results indicate that AGEs impair the neuroprotective effects of Sirt1 and lead to neuronal cell death via ER stress. Our findings suggest that AGEs increase ROS production, which stimulates downstream pathways related to APP processing, Aβ production, Sirt1, and GRP78, resulting in the up-regulation of cell death related pathway. This in-turn enhances neuronal cell death, which leads to the development of AD.
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spelling pubmed-46545232015-11-25 The Possible Mechanism of Advanced Glycation End Products (AGEs) for Alzheimer’s Disease Ko, Shun-Yao Ko, Hshin-An Chu, Kuo-Hsiung Shieh, Tzong-Ming Chi, Tzong-Cherng Chen, Hong-I Chang, Weng-Cheng Chang, Shu-Shing PLoS One Research Article Amyloid precursor protein (APP) has been modified by β and γ-secretase that cause amyloid deposits (plaques) in neuronal cells. Glyceraldhyde-derived AGEs has been identified as a major source of neurotoxicity in Alzheimer’s disease (AD). In a previous study, we demonstrated that glyceraldehyde-derived AGEs increase APP and Aβ via ROS. Furthermore, the combination of AGEs and Aβ has been shown to enhance neurotoxicity. In mice, APP expression is increased by tail vein injection of AGEs. This evidence suggests a correlation between AGEs and the development of AD. However, the role played by AGEs in the pathogenesis of AD remains unclear. In this report, we demonstrate that AGEs up-regulate APP processing protein (BACE and PS1) and Sirt1 expression via ROS, but do not affect the expression of downstream antioxidant genes HO-1 and NQO-1. Moreover, we found that AGEs increase GRP78 expression and enhance the cell death-related pathway p53, bcl-2/bax ratio, caspase 3. These results indicate that AGEs impair the neuroprotective effects of Sirt1 and lead to neuronal cell death via ER stress. Our findings suggest that AGEs increase ROS production, which stimulates downstream pathways related to APP processing, Aβ production, Sirt1, and GRP78, resulting in the up-regulation of cell death related pathway. This in-turn enhances neuronal cell death, which leads to the development of AD. Public Library of Science 2015-11-20 /pmc/articles/PMC4654523/ /pubmed/26587989 http://dx.doi.org/10.1371/journal.pone.0143345 Text en © 2015 Ko et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Ko, Shun-Yao
Ko, Hshin-An
Chu, Kuo-Hsiung
Shieh, Tzong-Ming
Chi, Tzong-Cherng
Chen, Hong-I
Chang, Weng-Cheng
Chang, Shu-Shing
The Possible Mechanism of Advanced Glycation End Products (AGEs) for Alzheimer’s Disease
title The Possible Mechanism of Advanced Glycation End Products (AGEs) for Alzheimer’s Disease
title_full The Possible Mechanism of Advanced Glycation End Products (AGEs) for Alzheimer’s Disease
title_fullStr The Possible Mechanism of Advanced Glycation End Products (AGEs) for Alzheimer’s Disease
title_full_unstemmed The Possible Mechanism of Advanced Glycation End Products (AGEs) for Alzheimer’s Disease
title_short The Possible Mechanism of Advanced Glycation End Products (AGEs) for Alzheimer’s Disease
title_sort possible mechanism of advanced glycation end products (ages) for alzheimer’s disease
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4654523/
https://www.ncbi.nlm.nih.gov/pubmed/26587989
http://dx.doi.org/10.1371/journal.pone.0143345
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