Development of a histochemical analytical system for metabolic enzymes of novel brain glycosylated sterols
Project/Area Number |
17KK0147
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Research Category |
Fund for the Promotion of Joint International Research (Fostering Joint International Research)
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Allocation Type | Multi-year Fund |
Research Field |
General medical chemistry
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Research Institution | Institute of Physical and Chemical Research |
Principal Investigator |
Akiyama Hisako 国立研究開発法人理化学研究所, 脳神経科学研究センター, 研究員 (80623462)
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Project Period (FY) |
2018 – 2020
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Project Status |
Completed (Fiscal Year 2020)
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Budget Amount *help |
¥14,560,000 (Direct Cost: ¥11,200,000、Indirect Cost: ¥3,360,000)
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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分解酵素 / 糖化 |
Outline of Final Research Achievements |
The glucosylceramide-degrading enzyme (GBA) is responsible for the synthesis and degradation of newly found glycosylated sterols (SGs) in the brain. Using a library of GBA inhibitors, I found that GBA exerts various SG metabolic activities using the same active site. I succeeded in detecting SGs in a region of less than 1 mm2 recovered from mouse brain sections using mass spectrometry. Since active GBA can be visualized by fluorescence modified inhibitor, superimposition of the localization of enzyme activity and enzyme reaction products will enable histochemical localization analysis of SG metabolic activities of GBA.
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Academic Significance and Societal Importance of the Research Achievements |
SG群の代謝を担うGBAは、その機能不全がパーキンソン病や小脳失調などの難治性神経変性疾患の原因となる。本研究で提案したGBAのSG代謝活性の組織化学的局在解析法を用いることで、SG代謝が難治性神経変性疾患発症の新たな分子基盤となり得る可能性を検証できるようになるため、本研究成果の学術的・社会的意義は大きい。
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Report
(4 results)
Research Products
(15 results)
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[Journal Article] Impact of GBA2 on neuronopathic Gaucher’s disease and α-synuclein accumulation in medaka (Oryzias latipes)2021
Author(s)
Nakanishi, E., Uemura, N., Akiyama, H., Kinoshita, M., Sawamura, M., Taruno, Y., Yamakado, H., Matsuzawa, S., Takeda, S., Hirabayashi, Y., and Takahashi, R.
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Journal Title
Molecular Brain
Volume: 未定
Related Report
Peer Reviewed
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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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[Journal Article] Role of β-glucosidase 2 in aberrant glycosphingolipid metabolism: model of glucocerebrosidase deficiency in zebrafish2019
Author(s)
Lelieveld, L. T., Mirzaian, M, Kuo, C-L., Artola M., Ferraz, M. J., Peter, R. E. A., Akiyama, H., Greimel, P., van den Berg, R. J. B. H. N., Overkleeft, H. S., Boot, R. G., Meijer, A. H., and Aerts, J. M. F. G.
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Journal Title
Journal of Lipid Research
Volume: 60
Issue: 11
Pages: 1851-1867
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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