| Project/Area Number |
17K17093
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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 |
Functional basic dentistry
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| Research Institution | Kyushu University |
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Principal Investigator |
NI JUNJUN 九州大学, 歯学研究院, 助教 (00783953)
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| Project Period (FY) |
2017-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2017: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | cathepsin B / lysosomal leakage / microglia / mitochondria / Alzheimer's disease / Microglia / Cathepsin E / 歯学 |
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| Outline of Final Research Achievements |
In this study, we found that genetic ablation of cathepsin B (CatB) in mice significantly reduced the generation of reactive oxygen species (ROS) and neuroinflammation and improved cognitive impairment during aging. Pharmacological inhibition of CatB significantly reduced the generation of mitochondria-derived ROS and proinflammatory mediators induced by L-leucyl-L-leucine methyl ester (LLOMe). In the CatB over-expressing microglia after treatment with LLOMe, which mimicked the aged microglia, CatB leaked in the cytosol is responsible for the degradation of the mitochondrial transcription factor A (TFAM), resulting in the increased generation of mitochondria-derived ROS and proinflammatory mediators through impaired mtDNA biosynthesis. These results suggest that the increase and leakage of CatB in microglia during aging are responsible for the increased generation of mitochondria-derived ROS and proinflammatory mediators, culminating in memory impairment.
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| Academic Significance and Societal Importance of the Research Achievements |
As the population ages and lifespan increases, the worldwide aging has become a sever society issue. Our study provides potential targets for slowing aging which will contribute to the healthy and slowed aging society.
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