title: Novel Lactulose and Melibiose Targeting Autophagy to Reduce PolyQ Aggregation in Cell Models of Spinocerebellar Ataxia 3.
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.
authors: Chih-Hsin
authors: CH
authors: Lin
authors: Yih-Ru
authors: YR
authors: Wu
authors: Jinn-Moon
authors: JM
authors: Yang
authors: Wan-Ling
authors: WL
authors: Chen
authors: Chih-Ying
authors: CY
authors: Chao
authors: I-Cheng
authors: IC
authors: Chen
authors: Te-Hsien
authors: TH
authors: Lin
authors: Yi-Ci
authors: YC
authors: Wu
authors: Kai-Cheng
authors: KC
authors: Hsu
authors: Chiung-Mei
authors: CM
authors: Chen
authors: Guan-Chiun
authors: GC
authors: Lee
authors: Hsiu-Mei
authors: HM
authors: Hsieh-Li
authors: Department of Life Science, National Taiwan Normal University, Taipei, Taiwan. t43003@ntnu.edu.tw.
authors: Chi-Mei
authors: CM
authors: Lee
authors: Guey-Jen
authors: GJ
authors: Lee-Chen
mesh_terms: D000704:Analysis of Variance; D000067699:Ataxin-3 / Q000235:genetics / Q000378:metabolism*; D001343:Autophagy / Q000187:drug effects* / Q000235:genetics; D045744:Cell Line, Tumor; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000235:genetics; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007792:Lactulose / Q000737:chemistry / Q000494:pharmacology*; D008553:Melibiose / Q000737:chemistry / Q000494:pharmacology*; D009447:Neuroblastoma / Q000473:pathology; D010455:Peptides / Q000235:genetics / Q000378:metabolism*; D066263:Protein Aggregation, Pathological / Q000188:drug therapy; D017382:Reactive Oxygen Species / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D014199:Trehalose / Q000494:pharmacology
chemical_list: D010455:Peptides; D017382:Reactive Oxygen Species; D012097:Repressor Proteins; D049452:Green Fluorescent Proteins; C097188:polyglutamine; D007792:Lactulose; D008553:Melibiose; D014199:Trehalose; C092341:ATXN3 protein, human; D000067699:Ataxin-3