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

Research output: Contribution to journalArticle

11 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)351-359
Number of pages9
JournalCNS and Neurological Disorders - Drug Targets
Volume15
Issue number3
Publication statusPublished - Apr 1 2016
Externally publishedYes

Keywords

  • ATXN3
  • Autophagy
  • Lactulose
  • Melibiose
  • Spinocerebellar ataxia
  • Trehalose

ASJC Scopus subject areas

  • Neuroscience(all)
  • Pharmacology

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  • Cite this

    Lin, C. H., Wu, Y. R., Yang, J. M., Chen, W. L., Chao, C. Y., Chen, I. C., Lin, T. H., Wu, Y. C., Hsu, K. C., Chen, C. M., Lee, G. C., Hsieh-Li, H. M., Lee, C. M., & Lee-Chen, G. J. (2016). Novel lactulose and melibiose targeting autophagy to reduce polyQ aggregation in cell models of spinocerebellar ataxia. CNS and Neurological Disorders - Drug Targets, 15(3), 351-359.