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.
