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dc.contributor.authorLee, Guan-Chiunen_US
dc.contributor.authorLin, Chih-Hsinen_US
dc.contributor.authorTao, Yu-Chenen_US
dc.contributor.authorYang, Jinn-Moonen_US
dc.contributor.authorHsu, Kai-Chengen_US
dc.contributor.authorHuang, Yin-Jungen_US
dc.contributor.authorHuang, Shih-Hanen_US
dc.contributor.authorKung, Pin-Juien_US
dc.contributor.authorChen, Wan-Lingen_US
dc.contributor.authorWang, Chien-Mingen_US
dc.contributor.authorWu, Yih-Ruen_US
dc.contributor.authorChen, Chiung-Meien_US
dc.contributor.authorLin, Jung-Yawen_US
dc.contributor.authorHsieh-Li, Hsiu Meien_US
dc.contributor.authorLee-Chen, Guey-Jenen_US
dc.date.accessioned2015-07-21T08:29:40Z-
dc.date.available2015-07-21T08:29:40Z-
dc.date.issued2015-05-01en_US
dc.identifier.issn0161-813Xen_US
dc.identifier.urihttp://dx.doi.org/10.1016/j.neuro.2015.03.009en_US
dc.identifier.urihttp://hdl.handle.net/11536/124829-
dc.description.abstractThe unique property of trehalose encourages its pharmaceutical application in aggregation-mediated neurodegenerative disorders, including Alzheimer\'s, Parkinson\'s, and many polyglutamine (polyQ)-mediated diseases. However, trehalose is digested into glucose by trehalase and which reduced its efficacy in the disease target tissues. Therefore, searching trehalase-indigestible analogs of trehalose is a potential strategy to enhance therapeutic effect. In this study, two trehalase-indigestible trehalose analogs, lactulose and melibiose, were selected through compound topology and functional group analyses. Hydrogen-bonding network analyses suggest that the elimination of the hydrogen bond between the linker ether and aspartate 321 (D321) of human trehalase is the key for lactulose and melibiose to avoid the hydrolyzation. Using polyQ-mediated spinocerebellar ataxia type 17 (SCA17) cell and slice cultures, we found the aggregation was significantly prohibited by trehalose, lactulose, and melibiose, which may through up-regulating of autophagy. These findings suggest the therapeutic applications of trehalase-indigestible trehalose analogs in aggregation-associated neurodegenerative diseases. (C) 2015 Elsevier Inc. All rights reserved.en_US
dc.language.isoen_USen_US
dc.subjectLactuloseen_US
dc.subjectMelibioseen_US
dc.subjectTrehalaseen_US
dc.subjectNeurodegenerative diseaseen_US
dc.subjectAutophagyen_US
dc.titleThe potential of lactulose and melibiose, two novel trehalase-indigestible and autophagy-inducing disaccharides, for polyQ-mediated neurodegenerative disease treatmenten_US
dc.typeArticleen_US
dc.identifier.doi10.1016/j.neuro.2015.03.009en_US
dc.identifier.journalNEUROTOXICOLOGYen_US
dc.citation.volume48en_US
dc.citation.spage120en_US
dc.citation.epage130en_US
dc.contributor.department生物資訊及系統生物研究所zh_TW
dc.contributor.departmentInstitude of Bioinformatics and Systems Biologyen_US
dc.identifier.wosnumberWOS:000355641600014en_US
dc.citation.woscount0en_US
Appears in Collections:Articles