| Budget Amount *help |
¥113,230,000 (Direct Cost: ¥87,100,000、Indirect Cost: ¥26,130,000)
Fiscal Year 2018: ¥20,410,000 (Direct Cost: ¥15,700,000、Indirect Cost: ¥4,710,000)
Fiscal Year 2017: ¥20,410,000 (Direct Cost: ¥15,700,000、Indirect Cost: ¥4,710,000)
Fiscal Year 2016: ¥20,540,000 (Direct Cost: ¥15,800,000、Indirect Cost: ¥4,740,000)
Fiscal Year 2015: ¥20,410,000 (Direct Cost: ¥15,700,000、Indirect Cost: ¥4,710,000)
Fiscal Year 2014: ¥31,460,000 (Direct Cost: ¥24,200,000、Indirect Cost: ¥7,260,000)
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| Outline of Final Research Achievements |
For the potential development of novel therapeutic strategies for tauopathies, our group established a tauopathy model bearing tau mutations associated with frontotemporal dementia with parkinsonism-17 (FTDP-17) for investigating tau pathology and for usage in drug screening.
For this purpose, we generated iPSCs from 2 frontotemporal dementia patients of a Japanese pedigree bearing the tau R406W mutation. To examine the phenotypes in neurons, we developed efficient cortical neural differentiation methods for iPSCs using small molecules. In this neuronal culture, the mutant tau exhibited reduced phosphorylation levels and was increasingly fragmented by calpain. Furthermore, the mutant tau protein was mislocalized and the axons of the patient-derived neurons displayed morphological and functional abnormalities, which were rescued by microtubule stabilization. Collectively, our findings provide new mechanistic insight into tau pathology and a potential for therapeutic intervention.
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