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

9 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

Fingerprint

Melibiose
Spinocerebellar Ataxias
Lactulose
Cell Aggregation
Autophagy
Trehalose
Trehalase
Tauopathies
Aptitude
Huntington Disease
Neurodegenerative Diseases
Parkinson Disease
Reactive Oxygen Species
Up-Regulation
polyglutamine
Therapeutics

Keywords

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

ASJC Scopus subject areas

  • Neuroscience(all)
  • Pharmacology

Cite this

Lin, C. H., Wu, Y. R., Yang, J. M., Chen, W. L., Chao, C. Y., Chen, I. C., ... 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.

Novel lactulose and melibiose targeting autophagy to reduce polyQ aggregation in cell models of spinocerebellar ataxia. / Lin, Chih Hsin; Wu, Yih Ru; Yang, Jinn Moon; Chen, Wan Ling; Chao, Chih Ying; Chen, I. Cheng; Lin, Te Hsien; Wu, Yi Ci; Hsu, Kai Cheng; Chen, Chiung Mei; Lee, Guan Chiun; Hsieh-Li, Hsiu Mei; Lee, Chi Mei; Lee-Chen, Guey Jen.

In: CNS and Neurological Disorders - Drug Targets, Vol. 15, No. 3, 01.04.2016, p. 351-359.

Research output: Contribution to journalArticle

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.
Lin, Chih Hsin ; Wu, Yih Ru ; Yang, Jinn Moon ; Chen, Wan Ling ; Chao, Chih Ying ; Chen, I. Cheng ; Lin, Te Hsien ; Wu, Yi Ci ; Hsu, Kai Cheng ; Chen, Chiung Mei ; Lee, Guan Chiun ; Hsieh-Li, Hsiu Mei ; Lee, Chi Mei ; Lee-Chen, Guey Jen. / Novel lactulose and melibiose targeting autophagy to reduce polyQ aggregation in cell models of spinocerebellar ataxia. In: CNS and Neurological Disorders - Drug Targets. 2016 ; Vol. 15, No. 3. pp. 351-359.
@article{4f5d2f3278b3447dad3cbe8876d393c7,
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’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.",
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}",
year = "2016",
month = "4",
day = "1",
language = "English",
volume = "15",
pages = "351--359",
journal = "CNS and Neurological Disorders - Drug Targets",
issn = "1871-5273",
publisher = "Bentham Science Publishers B.V.",
number = "3",

}

TY - JOUR

T1 - Novel lactulose and melibiose targeting autophagy to reduce polyQ aggregation in cell models of spinocerebellar ataxia

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

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

UR - http://www.scopus.com/inward/record.url?scp=84961589973&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84961589973&partnerID=8YFLogxK

M3 - Article

C2 - 26295831

AN - SCOPUS:84961589973

VL - 15

SP - 351

EP - 359

JO - CNS and Neurological Disorders - Drug Targets

JF - CNS and Neurological Disorders - Drug Targets

SN - 1871-5273

IS - 3

ER -