标题: | The potential of lactulose and melibiose, two novel trehalase-indigestible and autophagy-inducing disaccharides, for polyQ-mediated neurodegenerative disease treatment |
作者: | Lee, Guan-Chiun Lin, Chih-Hsin Tao, Yu-Chen Yang, Jinn-Moon Hsu, Kai-Cheng Huang, Yin-Jung Huang, Shih-Han Kung, Pin-Jui Chen, Wan-Ling Wang, Chien-Ming Wu, Yih-Ru Chen, Chiung-Mei Lin, Jung-Yaw Hsieh-Li, Hsiu Mei Lee-Chen, Guey-Jen 生物资讯及系统生物研究所 Institude of Bioinformatics and Systems Biology |
关键字: | Lactulose;Melibiose;Trehalase;Neurodegenerative disease;Autophagy |
公开日期: | 1-五月-2015 |
摘要: | The 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. |
URI: | http://dx.doi.org/10.1016/j.neuro.2015.03.009 http://hdl.handle.net/11536/124829 |
ISSN: | 0161-813X |
DOI: | 10.1016/j.neuro.2015.03.009 |
期刊: | NEUROTOXICOLOGY |
Volume: | 48 |
起始页: | 120 |
结束页: | 130 |
显示于类别: | Articles |