Transgutaminases in gial cells and neurodegenerative diseases
| Project/Area Number |
17K15390
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Integrative animal science
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| Research Institution | Osaka Prefecture University |
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Principal Investigator |
Takano Katsura 大阪府立大学, 生命環境科学研究科, 准教授 (50453139)
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| Project Period (FY) |
2017-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2017: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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| Keywords | ミクログリア / アストロサイト / トランスグルタミナーゼ / 神経変性疾患 / アルツハイマー病 / アミロイドβ |
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| Outline of Final Research Achievements |
Transglutaminase (TG) is a crosslinking enzyme and contributes to various physiological functions. TGs have 8 isozymes and TG2 among them is unique as multifunctional enzyme. TG2 is normally expressed at low levels and activated under various pathological conditions. In CNS, TGs are expressed in neurons and glial cells. It has been shown that TGs are aberrantly-activated in neurodegenerative diseases including Alzheimer’s. Increased TG activity may contribute to the formation of insoluble deposits; however, the mechanisms remain to be clarified. On the other hand, it also has been shown that aberrant activation of glia; excessive production of nitric oxide and inflammatory cytokines, phagocytosis of viable neurons, and so on, causes neurodegeneration. We demonstrated that TG2 was upregulated in astrocytes and microglia by activation and involved in glial functions such as inflammation and endocytosis. Therefore, TGs might be a novel therapeutic target for neurodegeneration.
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| Academic Significance and Societal Importance of the Research Achievements |
グリア細胞の機能制御が正常な脳内環境の維持に重要であることは周知の事実となりつつあり、グリア細胞の炎症反応を単に抑制する化合物は報告されているが、対症療法にすぎない。TGsは神経変性疾患での発現上昇などは知られているものの、グリア細胞での発現およびその機能についての報告は少ない。また、TGs活性阻害剤がハンチントン病モデル動物において症状軽減および延命効果があるとの報告もあり、TGsは新規の脳疾患治療薬のターゲットとなりうる。本研究成果により、グリア細胞におけるTGsの発現および機能調節機構が解明されれば、神経変性疾患における神経細胞死を保護する新たな薬剤の開発につながることが期待される。
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Report
(5 results)
Research Products
(23 results)
