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

doi:10.2174/1871527314666150821101522

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

^*Corresponding author for this work

Department of Life Science

Research output: Contribution to journal › Article › peer-review

18 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 language	English
Pages (from-to)	351-359
Number of pages	9
Journal	CNS and Neurological Disorders - Drug Targets
Volume	15
Issue number	3
DOIs	https://doi.org/10.2174/1871527314666150821101522
Publication status	Published - 2016 Apr 1

Keywords

ATXN3
Autophagy
Lactulose
Melibiose
Spinocerebellar ataxia
Trehalose

ASJC Scopus subject areas

Neuroscience(all)
Pharmacology

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10.2174/1871527314666150821101522

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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. https://doi.org/10.2174/1871527314666150821101522

Lin, CH, Wu, YR, Yang, JM, Chen, WL, Chao, CY, Chen, IC, Lin, TH, Wu, YC, Hsu, KC, Chen, CM, Lee, GC , Hsieh-Li, HM, Lee, CM & Lee-Chen, GJ 2016, 'Novel lactulose and melibiose targeting autophagy to reduce polyQ aggregation in cell models of spinocerebellar ataxia', CNS and Neurological Disorders - Drug Targets, vol. 15, no. 3, pp. 351-359. https://doi.org/10.2174/1871527314666150821101522

@article{5d944b81ad064b9491552cb2638a73fe,

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

abstract = "Trehalose, a chemical chaperone and mTOR-independent autophagy enhancer, has shown promise in models of Huntington{\textquoteright}s disease, Parkinson{\textquoteright}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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author = "Lin, {Chih Hsin} and Wu, {Yih Ru} and Yang, {Jinn Moon} and Chen, {Wan Ling} and Chao, {Chih Ying} and Chen, {I. Cheng} and Lin, {Te Hsien} and Wu, {Yi Ci} and Hsu, {Kai Cheng} and Chen, {Chiung Mei} and Lee, {Guan Chiun} and Hsieh-Li, {Hsiu Mei} and Lee, {Chi Mei} and Lee-Chen, {Guey Jen}",

note = "Funding Information: We thank the Molecular Imaging Core Facility of National Taiwan Normal University and the Core Facilities for Protein Structural Analysis of National Research Program for Biopharmaceuticals (NRPB) from the National Science Council, Executive Yuan for the technical assistance. We also gratefully acknowledge Dr. Cheng-Chung Lee for his helpful opinions and discussions. This work was supported by the grants 102-2325-B-003-002, 102-2314-B-182A-113-MY2, 103-2811-B-182A-007 and 103-2325-B-003-001 from the Ministry of Science and Technology, Taipei, Taiwan Publisher Copyright: {\textcopyright} 2016 Bentham Science Publishers.",

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doi = "10.2174/1871527314666150821101522",

language = "English",

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AU - Lin, Chih Hsin

AU - Wu, Yih Ru

AU - Yang, Jinn Moon

AU - Chen, Wan Ling

AU - Chao, Chih Ying

AU - Chen, I. Cheng

AU - Lin, Te Hsien

AU - Wu, Yi Ci

AU - Hsu, Kai Cheng

AU - Chen, Chiung Mei

AU - Lee, Guan Chiun

AU - Hsieh-Li, Hsiu Mei

AU - Lee, Chi Mei

AU - Lee-Chen, Guey Jen

N1 - Funding Information: We thank the Molecular Imaging Core Facility of National Taiwan Normal University and the Core Facilities for Protein Structural Analysis of National Research Program for Biopharmaceuticals (NRPB) from the National Science Council, Executive Yuan for the technical assistance. We also gratefully acknowledge Dr. Cheng-Chung Lee for his helpful opinions and discussions. This work was supported by the grants 102-2325-B-003-002, 102-2314-B-182A-113-MY2, 103-2811-B-182A-007 and 103-2325-B-003-001 from the Ministry of Science and Technology, Taipei, Taiwan Publisher Copyright: © 2016 Bentham Science Publishers.

PY - 2016/4/1

Y1 - 2016/4/1

N2 - 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.

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

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Keywords

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