| Project Area | Prevention of brain protein aging and dementia |
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| Project/Area Number |
26117004
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| Research Category |
Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
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| Allocation Type | Single-year Grants |
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| Review Section |
Biological Sciences
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| Research Institution | Gakushuin University (2016-2018)
National Center for Geriatrics and Gerontology (2014-2015) |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
久永 眞市 首都大学東京, 理学研究科, 客員教授 (20181092)
石垣 診祐 名古屋大学, 医学系研究科, 特任准教授 (40378170)
宮坂 知宏 同志社大学, 生命医科学部, 准教授 (90342857)
池川 雅哉 同志社大学, 生命医科学部, 教授 (60381943)
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| Research Collaborator |
Soeda Yoshiyuki
Sumioka Akio
Misonou Hiroaki
Taguchi Akiko
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| Project Period (FY) |
2014-07-10 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥237,250,000 (Direct Cost: ¥182,500,000、Indirect Cost: ¥54,750,000)
Fiscal Year 2018: ¥45,110,000 (Direct Cost: ¥34,700,000、Indirect Cost: ¥10,410,000)
Fiscal Year 2017: ¥44,980,000 (Direct Cost: ¥34,600,000、Indirect Cost: ¥10,380,000)
Fiscal Year 2016: ¥45,110,000 (Direct Cost: ¥34,700,000、Indirect Cost: ¥10,410,000)
Fiscal Year 2015: ¥44,850,000 (Direct Cost: ¥34,500,000、Indirect Cost: ¥10,350,000)
Fiscal Year 2014: ¥57,200,000 (Direct Cost: ¥44,000,000、Indirect Cost: ¥13,200,000)
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| Keywords | タウタンパク質 / Aβ / 老化 / 認知症 / 脳機能 / 凝集 / リン酸化 / 神経細胞死 / 神経科学 / 脳神経疾患 / タウ / 局在 / 過活動 / 樹状突起 |
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| Outline of Final Research Achievements |
Tau gene express six isoforms by alternative splicing. Among them, we appears that 3R and 4R tau play different roles in adult neurogenesis, which may cause the onset of dementia. Although rodents convert 3R tau to 4R tau in adult, but in adult humans, 3R tau is still expressed as much as 4R tau. In case of marmoset used as a human model, tau is different from human in terms of tau isoform expression in adulthood.
Although tau is known as microtubule protein, our study revealed that tau is involved in receptor endocytosis as a synaptic protein. In particular, in hyperactive neurons, tau may decrease the number of receptor on post-synapse, and provide neuroprotection from neuronal hyperactivity. The robustness of this neurons may eventually be linked to the accumulation of phosphorylated tau to the formation of granular tau oligomers as a pathogenic protein. Further studies are needed for clarifying these points based on this conclusion for developing new therapy for dementia.
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| Academic Significance and Societal Importance of the Research Achievements |
タウタンパク質は1975年微小管結合タンパク質として精製されて以来、その機能について全貌は明らかにされていない。アルツハイマー病の特徴的な病理像の一つとして神経原線維変化が見出され、この病理像を示す領域は臨床症状の責任病巣とよく相関する。主な構成成分が過剰にリン酸化されたタウである。近年、タウを標的とした治療法開発が注目を浴びている。この研究成果はタウタンパク質の新たな役割がシナプス機能にあること、顆粒状タウオリゴマーが病原タンパクであること、タウアイソフォームは成体神経新生において異なる役割を果たすことを示しており、βアミロイド以外の新たな認知症治療標的分子の探索に大きく寄与するものである。
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