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Lookup NU author(s): Rhianna RowlandORCiD
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND).
Gaucher disease is caused by inherited deficiency in glucocerebrosidase (GBA, a retaining β-glucosidase), and deficiency in GBA constitutes the largest known genetic risk factor for Parkinson’s disease. In the past, animal models of Gaucher disease have been generated by treatment with the mechanism-based GBA inhibitors, conduritol B epoxide (CBE), and cyclophellitol. Both compounds, however, also target other retaining glycosidases, rendering generation and interpretation of such chemical knockout models complicated. Here we demonstrate that cyclophellitol derivatives carrying a bulky hydrophobic substituent at C8 are potent and selective GBA inhibitors and that an unambiguous Gaucher animal model can be readily generated by treatment of zebrafish with these.
Author(s): Artola M, Kuo CL, Lelieveld LT, Rowland RJ, van der Marel GA, Codee JDC, Boot RG, Davies GJ, Aerts JMFG, Overkleeft HS
Publication type: Article
Publication status: Published
Journal: Journal of the American Chemical Society
Print publication date: 13/03/2019
Online publication date: 27/02/2019
Acceptance date: 02/04/2018
Date deposited: 24/01/2022
ISSN (print): 0002-7863
ISSN (electronic): 1520-5126
Publisher: American Chemical Society
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