Reconstruction of sterol metabolic pathways based on the discovery of novel glycosylated sterols in the brain
| Project/Area Number |
16K14687
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Structural biochemistry
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| Research Institution | Institute of Physical and Chemical Research |
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Principal Investigator |
Hirabayashi Yoshio 国立研究開発法人理化学研究所, 開拓研究本部, 客員主管研究員 (90106435)
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| Project Period (FY) |
2016-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2018: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | ステロール / 糖化ステロール / 糖脂質 / グルコシルセラミド / 脳内ステロール代謝 / 神経変性疾患 |
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| Outline of Final Research Achievements |
We focused on novel sterol metabolites, glycosylated sterols that we discovered in vertebrate brain, and verified whether unreported sterol metabolic pathways exist in the brain. Structural analysis of the glycosylated sterols revealed for the first time that glycolipids, in which glucose and galactose are bound to cholesterol and a plant sterol, are present in the brain. Their synthesis and degradation were found to be mediated by glucosylceramide-degrading enzymes, whose involvement in sterol metabolism was not previously reported.
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| Academic Significance and Societal Importance of the Research Achievements |
脳内新規糖化ステロール群の合成・分解を担うことが明らかになったグルコシルセラミド分解酵素は、その機能不全がパーキンソン病や小脳失調などの神経変性疾患の原因となる。脳内新規糖化ステロール群の代謝調節という新しい機能に着目することにより、グルコシルセラミド分解酵素の機能不全が神経変性疾患を引き起こすメカニズムを明らかにすることできる可能性があり、本研究成果の学術的・社会的意義は大きい。
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Report
(5 results)
Research Products
(18 results)
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[Journal Article] Glucocerebrosidases catalyze a transgalactosylation reaction that yields a newly-identified brain sterol metabolite, galactosylated cholesterol2020
Author(s)
Akiyama, H., Ide, M., Nagatsuka, Y., Sayano, T., Nakanishi, E., Uemura, N., Yuyama, K., Yamaguchi, Y., Kamiguchi, H., Takahashi, R., Aerts, J. M. F. G., Greimel, P. and Hirabayashi, Y
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Journal Title
Journal of Biological Chemistry
Volume: 295
Issue: 16
Pages: 5257-5277
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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