Atriazole derivative elicits autophagic clearance of polyglutamine aggregation in neuronal cells

Chang Heng Hsieh, Li Ching Lee, Wai Yin Leong, Tsai Chen Yang, Ching Fa Yao, Kang Fang

研究成果: 雜誌貢獻文章

2 引文 斯高帕斯(Scopus)

摘要

Trinucleotide CAG repeat expansion in the coding region of genes has a propensity to form polyglutamine (polyQ) aggregates that contribute to neuronal disorders. Strategies in elevating autophagy to disintegrate the insoluble aggregates without injuring cells have become a major goal for therapy. In this work, a triazole derivative, OC-13, was found accelerating autophagic clearance of polyQ aggregation in human neuroblastoma cells following induction of the enhanced green fluorescence-conjugated chimeric protein that enclosed 79 polyQ repeats (Q79-EGFP). OC-13 accelerated autophagy development and removed nuclear Q79-EGFP aggregates. The increase of Beclin-1, turnover of LC3-I to LC3-II and degradation of p62 supported autophagy activation. Pretreatment of autophagy inhibitor, bafilomycin A1, not only suppressed autophagolysome fusion, but also impeded aggregate eradication. The study also showed that c-Jun N-terminal kinase/Beclin-1 pathway was activated during OC-13 treatment and c-Jun N-terminal kinase inhibitor impaired autophagy and final breakdown. Autophagic clearance of the insoluble aggregates demonstrated the feasibility of OC-13 in alleviating neuronal disorders because of expanded glutamine stretches.

原文英語
頁(從 - 到)2947-2957
頁數11
期刊Drug Design, Development and Therapy
10
DOIs
出版狀態已發佈 - 2016 九月 14

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science
  • Drug Discovery

指紋 深入研究「Atriazole derivative elicits autophagic clearance of polyglutamine aggregation in neuronal cells」主題。共同形成了獨特的指紋。

  • 引用此