標題: 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
生物資訊及系統生物研究所
Institude of Bioinformatics and Systems Biology
關鍵字: Lactulose;Melibiose;Trehalase;Neurodegenerative disease;Autophagy
公開日期: 1-May-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
起始頁: 120
結束頁: 130
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