PloS one, 2015-11, Vol.10 (11), p.e0143345
2015
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Details
- Autor(en) / Beteiligte
- Titel
- The Possible Mechanism of Advanced Glycation End Products (AGEs) for Alzheimer's Disease
- Ist Teil von
- PloS one, 2015-11, Vol.10 (11), p.e0143345
- Ort / Verlag
- United States: Public Library of Science
- Erscheinungsjahr
- 2015
- Quelle
- Free E-Journal (出版社公開部分のみ）
- Beschreibungen/Notizen
- 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1932-6203eISSN: 1932-6203DOI: 10.1371/journal.pone.0143345Titel-ID: cdi_plos_journals_1735002524
- Format
- –
- Schlagworte
- Advanced glycation end products, Advanced glycosylation end products, Age, Alzheimer Disease - etiology, Alzheimer Disease - metabolism, Alzheimer's disease, Amyloid beta-protein, Amyloid beta-Protein Precursor - metabolism, Amyloid precursor protein, Amyloid Precursor Protein Secretases - metabolism, Antioxidants, Antioxidants - chemistry, Apoptosis, Aspartic Acid Endopeptidases - metabolism, BAX protein, Bcl-2 protein, Caspase, Caspase 3 - metabolism, Caspase-3, Cell Death, Cell Line, Tumor, Development and progression, Endoplasmic reticulum, Endoplasmic Reticulum Stress, Gene expression, Gene Expression Regulation, Genetic aspects, Glycation End Products, Advanced - metabolism, Glyceraldehyde, Glycosylation, Heat-Shock Proteins - metabolism, Humans, Immunoglobulins, Medical research, Medicine, Mortality, Neuroblastoma, Neurodegenerative diseases, Neurons - pathology, Neuroprotection, Neuroprotective Agents, Neurotoxicity, Oxidative stress, p53 Protein, Pathogenesis, Penicillin, Physiological aspects, Plaque, Amyloid - pathology, Plaques, Presenilin 1, Presenilin-1 - metabolism, Proto-Oncogene Proteins c-bcl-2 - metabolism, Reactive Oxygen Species - metabolism, Rodents, Science, Secretase, SIRT1 protein, Sirtuin 1 - metabolism, Stilbenes - chemistry, Studies, Tumor Suppressor Protein p53 - metabolism, Up-Regulation, β-Site APP-cleaving enzymes