Identification of novel mechanisms of alcohol-related dementia
| Project/Area Number |
18KK0258
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| Research Category |
Fund for the Promotion of Joint International Research (Fostering Joint International Research (B))
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| Allocation Type | Multi-year Fund |
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| Review Section |
Medium-sized Section 57:Oral science and related fields
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| Research Institution | Niigata University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
岸川 咲吏 福岡歯科大学, 口腔歯学部, 助教 (50781358)
飯田 和泉 (渡辺和泉) 新潟大学, 医歯学系, 助教 (80751031)
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| Project Period (FY) |
2018-10-09 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥17,940,000 (Direct Cost: ¥13,800,000、Indirect Cost: ¥4,140,000)
Fiscal Year 2021: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2020: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2019: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2018: ¥6,760,000 (Direct Cost: ¥5,200,000、Indirect Cost: ¥1,560,000)
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| Keywords | アストロサイト / アルツハイマー病 / アルコール / 認知機能 / アンモニア |
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| Outline of Final Research Achievements |
Chronic alcohol consumption can lead to the development of hyperammonemia due to liver dysfunction. We identified that liver failure-associated hyperammonemia induces neuroinflammation which can be described by the increased number of reactive astrocytes in the brain. We also identified that ammonia stimulation induces the production of amyloid beta, a critical initiator that triggers the progression of Alzheimer’s disease. Using primary cultured astrocytes prepared from rat embryo, we found the mechanisms of amyloid beta production; ammonia enhances amyloid precursor protein (APP) endocytosis from the plasma membrane, induces transportation of APP to the endoplasmic reticulum, where two enzymes cleave APP to generate amyloid beta peptides. We reported these mechanisms as a novel mechanism driving Alzheimer’s disease.
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| Academic Significance and Societal Importance of the Research Achievements |
アミロイドβはアルツハイマー病の原因因子として長年注目されてきているが、神経細胞が産生し、細胞外に排出することで脳内に蓄積され、それが病理学的所見として観察されていると考えられてきた。研究代表者が本研究で見出したのは、脳内で最も数が多いグリア細胞であるアストロサイトがアミロイドβを産生する機構であり、新規の病態発症機序と考えられる。本研究での高アンモニア血症によるアルツハイマー病の発症の可能性を示す研究データは、日常生活においても高タンパク食の食事などでも起こり得る高アンモニア血症とアルツハイマー病との関連性を示すものであり、社会的意義が大きいと考える。
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Report
(5 results)
Research Products
(35 results)
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[Journal Article] Drug-induced naive iPS cells exhibit better performance than primed iPS cells with respect to the ability to differentiate into pancreatic β-cell lineage2020
Author(s)
Kiyokawa Y, Sato M, Noguchi H, Inada E, Iwase Y, Kubota N, Sawami T, Terunuma M, Maeda T, Hayasaki H, Saitoh I
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Journal Title
Journal of Clinical Medicine
Volume: 9
Issue: 9
Pages: 2838-2838
DOI
Related Report
Peer Reviewed / Open Access
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