2018 Fiscal Year Annual Research Report
The enzymatic activity of Cathepsin E in Abeta degradation
| Project/Area Number |
17K17093
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| Research Institution | Kyushu University |
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Principal Investigator |
倪 軍軍 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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| Keywords | cathepsin B / lysosomal leakage / microglia / mitochondria |
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| Outline of Annual Research Achievements |
We found that cathepsin B (CatB) deficiency in mice significantly reduced the generation of reactive oxygen species (ROS) and neuroinflammation and improved cognitive impairment during aging. In the CatB over-expressing microglia after treatment with LLOMe, 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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