Novel lactulose and melibiose targeting autophagy to reduce polyQ aggregation in cell models of spinocerebellar ataxia

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*, Guey Jen Lee-Chen

*此作品的通信作者

研究成果: Article同行評審

13 引文 斯高帕斯(Scopus)

摘要

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.

原文English
頁(從 - 到)351-359
頁數9
期刊CNS and Neurological Disorders - Drug Targets
15
發行號3
DOIs
出版狀態Published - 1 四月 2016

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