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

^*此作品的通信作者

生命科學系

研究成果: 雜誌貢獻 › 期刊論文 › 同行評審

24 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	英語
頁（從 - 到）	351-359
頁數	9
期刊	CNS and Neurological Disorders - Drug Targets
卷	15
發行號	3
DOIs	https://doi.org/10.2174/1871527314666150821101522
出版狀態	已發佈 - 2016 4月 1

ASJC Scopus subject areas

一般神經科學
藥理

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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, 卷 15, 編號 3, 頁 351-359. https://doi.org/10.2174/1871527314666150821101522

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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.",

keywords = "ATXN3, Autophagy, Lactulose, Melibiose, Spinocerebellar ataxia, Trehalose",

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}",

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year = "2016",

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doi = "10.2174/1871527314666150821101522",

language = "English",

volume = "15",

pages = "351--359",

journal = "CNS and Neurological Disorders - Drug Targets",

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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

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.

KW - ATXN3

KW - Autophagy

KW - Lactulose

KW - Melibiose

KW - Spinocerebellar ataxia

KW - Trehalose

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

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