2021 Fiscal Year Final Research Report
Preventive strategy against Alzheimer's disease by metallothionein induction
Project/Area Number |
19H03374
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 一般 |
Review Section |
Basic Section 47030:Pharmaceutical hygiene and biochemistry-related
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Research Institution | University of Shizuoka |
Principal Investigator |
Takeda Atsushi 静岡県立大学, 薬学部, 客員教授 (90145714)
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Project Period (FY) |
2019-04-01 – 2022-03-31
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Keywords | 亜鉛 / アミロイドβ / アルツハイマー病 / メタロチオネイン |
Outline of Final Research Achievements |
Human amyloid-β1-42 (Aβ1-42), a causative peptide in Alzheimer’s disease pathogenesis captures extracellular Zn2+ and readily taken up into hippocampal neurons followed by intracellular Zn2+ dysregulation. In contrast, metallothioneins, zinc-binding proteins can capture Zn2+ released from intracellular Zn-Aβ1-42 complexes, resulting in protection of hippocampal neurodegeneration by Aβ1-42-induced Zn2+ toxicity. The present study indicates that pre-administration of Ninjin-yoei-to, a Kampo medicine and dehydroeffusol, a phenanthrene isolated from Juncus effusus prevent Aβ1-42-mediated neurodegeneration in the dentate gyurs by induced synthesis of metallothioneins, which reduces intracellular Zn2+ toxicity induced by Aβ1-42. Ninjin-yoei-to and dehydroeffusol, novel inducers of metallothioneins, may protect Aβ1-42-induced pathogenesis in Alzheimer’s disease.
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Free Research Field |
神経科学
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Academic Significance and Societal Importance of the Research Achievements |
細胞内亜鉛恒常性に関与するメタロチオネイン(MT)を脳内で誘導合成することにより、Aβ1-42由来のZn2+毒性が軽減し、海馬神経細胞死が阻止できることを実験動物で示すことに成功した。MT誘導合成のために経口投与される人参養栄湯、デヒドロエフソールは自発運動量などに影響を与えない毒性の低い物質である。本研究成果は、アルツハイマー病発症を予防する独創的、かつ斬新的なものであり、超高齢社会である日本でのアルツハイマー病の予防戦略として大いに期待される。
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