2016 Fiscal Year Final Research Report
Participation of aberrant ketone body metabolism in pathogenic mechanism of cognitive dysfunction
| Project/Area Number |
15K18911
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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 |
Environmental and hygienic pharmacy
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| Research Institution | Hoshi University |
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Principal Investigator |
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| Project Period (FY) |
2015-04-01 – 2017-03-31
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| Keywords | ケトン体 / アセトアセチルCoA合成酵素 / レグマイン / 神経機能 / 神経伝達物質 / ノルエピネフリン |
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| Outline of Final Research Achievements |
Acetoacetyl-CoA synthetase (AACS) is a ketone body-utilizing enzyme and is responsible for the synthesis of cholesterol and fatty acids. In this study, we showed that Asn547 is specific cleavage site of AACS by legumain, which is a lysosomal asparaginyl endopeptidase and is activated in the brain with Alzheimer’s disease. The cleavage of AACS by legumain is critical for the regulation of enzymatic activity. Moreover, knockout of AACS caused a decrease in gene expression of dopamine-beta-hydroxylase; witch catalyzes the conversion of dopamine to norepinephrine. These results suggest that AACS has an important role for neurotransmitter metabolism and neurogenesis. Taken together, changes of AACS activity may relate to pathogenic mechanism of Alzheimer’s disease.
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| Free Research Field |
衛生化学・分子生物学
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