2021 Fiscal Year Final Research Report
Elucidation of the mechanism in Alzheimer's disease through advanced glycation end products by glyceraldehyde
Project/Area Number |
19K11781
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 59040:Nutrition science and health science-related
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Research Institution | Suzuka University of Medical Science |
Principal Investigator |
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Co-Investigator(Kenkyū-buntansha) |
古川 絢子 鈴鹿医療科学大学, 薬学部, 助教 (10455537)
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Project Period (FY) |
2019-04-01 – 2022-03-31
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Keywords | アルツハイマー病 / 神経原線維変化 / 終末糖化産物 / βチューブリン |
Outline of Final Research Achievements |
Diabetes mellitus (DM) has been identified as a risk factor for the onset and progression of Alzheimer’s disease (AD). In our previous study, we demonstrated that glyceraldehyde (GA)-derived toxic advanced glycation end-products (toxic AGEs, TAGE) induced similar alterations to those observed in AD. In another study, we identified TAGE in the cell bodies of neurons in the hippocampus and parahippocampal gyrus of the brains of AD patients. GA induced dysfunctional neurite outgrowth via TAGE-β-tubulin aggregation, which resulted in the TAGE-dependent abnormal aggregation of β-tubulin and tau phosphorylation in human neuroblastoma SH-SY5Y cells.
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Free Research Field |
神経化学
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Academic Significance and Societal Importance of the Research Achievements |
申請者らはこれまで、ブドウ糖果糖液糖(コーンシロップ)含有飲食物の過剰摂取による グリセルアルデヒド(GA) の蓄積が糖尿病の発症やアルツハイマー型認知症(AD) 様の強い中枢神経障害を引き起こす可能性を報告してきた。これまでの研究から、GA は細胞内タンパク質と反応して GA 由来の終末糖化産物(Glycer-AGEs) の生成/蓄積を介して強い中枢神経変性を引き起こすことが分ってきた。独自のGlycer-AGEs 抗体を用いた予試験的なスクリーニングにより、βチューブリンが GA によりAGE 化されて異常な重合を示すことが分った。
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