Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2012: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
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Outline of Final Research Achievements |
To treat Alzheimer's disease, it is required to reduce the amount of amyloid-β peptide in the brain. γ-Secretase prefer phosphorylated C-terminal fragments of precursor protein of amyloid-β peptide (APP) as a substrate. To identify the molecules related with APP phosphorylation, DYRK1A (dual-specificity tyrosine-(Y)-phosphorylation-regulated kinase 1A) and RCAN1 (regulator of calcineurin 1) on chromosome 21 were focused. Overexpression of DYRK1A leaded to APP and tau phosphorylation, while overexpression of RCAN1 leaded to tau phosphorylation, but not APP. Moreover, overexpression of either or both leaded to decrease in the peptidase activity of neprilysin and increase in of the phosphorylation of neprilysin. Treatment of a DYRK1A inhibitor reduced Aβ levels in the medium. These results suggest that DYRK1A and RCAN1A are potential targets of drug development to treatment of Alzheimer's disease.
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