Abstract
Trehalose, a chemical chaperone and mTOR-independent autophagy enhancer, has shown promise in models of Huntington’s disease, Parkinson’s disease and tauopathies. In this study, two trehalase analogs, lactulose and melibiose, were examined for their potentials in spinocerebellar ataxia treatment. Using a SCA3 ATXN3/Q75-GFP cell model, we found that the ATXN3/Q75 aggregation was significantly prohibited by lactulose and melibiose because of their abilities to up-regulate autophagy. Meanwhile, lactulose and melibiose reduced reactive oxygen species production in ATXN3/Q75 cells. Both of them further inhibited the ATXN3/Q75 aggregation in neuronally differentiated SH-SY5Y cells. These findings suggest the therapeutic applications of novel trehalose analogs in polyglutamine aggregation-associated neurodegenerative diseases.
Keywords: ATXN3, autophagy, lactulose, melibiose, spinocerebellar ataxia, trehalose.
CNS & Neurological Disorders - Drug Targets
Title:Novel Lactulose and Melibiose Targeting Autophagy to Reduce PolyQ Aggregation in Cell Models of Spinocerebellar Ataxia 3
Volume: 15 Issue: 3
Author(s): Chih-Hsin Lin, Yih-Ru Wu, Jinn-Moon Yang, Wan-Ling Chen, Chih-Ying Chao, I-Cheng Chen, Te-Hsien Lin, Yi-Ci Wu, Kai-Cheng Hsu, Chiung-Mei Chen, Guan-Chiun Lee, Hsiu-Mei Hsieh-Li, Chi-Mei Lee and Guey-Jen Lee-Chen
Affiliation:
Keywords: ATXN3, autophagy, lactulose, melibiose, spinocerebellar ataxia, trehalose.
Abstract: Trehalose, a chemical chaperone and mTOR-independent autophagy enhancer, has shown promise in models of Huntington’s disease, Parkinson’s disease and tauopathies. In this study, two trehalase analogs, lactulose and melibiose, were examined for their potentials in spinocerebellar ataxia treatment. Using a SCA3 ATXN3/Q75-GFP cell model, we found that the ATXN3/Q75 aggregation was significantly prohibited by lactulose and melibiose because of their abilities to up-regulate autophagy. Meanwhile, lactulose and melibiose reduced reactive oxygen species production in ATXN3/Q75 cells. Both of them further inhibited the ATXN3/Q75 aggregation in neuronally differentiated SH-SY5Y cells. These findings suggest the therapeutic applications of novel trehalose analogs in polyglutamine aggregation-associated neurodegenerative diseases.
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Lin Chih-Hsin, Wu Yih-Ru, Yang Jinn-Moon, Chen Wan-Ling, Chao Chih-Ying, Chen I-Cheng, Lin Te-Hsien, Wu Yi-Ci, Hsu Kai-Cheng, Chen Chiung-Mei, Lee Guan-Chiun, Hsieh-Li Hsiu-Mei, Lee Chi-Mei and Lee-Chen Guey-Jen, Novel Lactulose and Melibiose Targeting Autophagy to Reduce PolyQ Aggregation in Cell Models of Spinocerebellar Ataxia 3, CNS & Neurological Disorders - Drug Targets 2016; 15 (3) . https://dx.doi.org/10.2174/1871527314666150821101522
DOI https://dx.doi.org/10.2174/1871527314666150821101522 |
Print ISSN 1871-5273 |
Publisher Name Bentham Science Publisher |
Online ISSN 1996-3181 |
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