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Small molecule regulators of autophagy identified by an image-based high-throughput screen.

Small molecule regulators of autophagy identified by an image-based high-throughput screen. Research Abstract Details 

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  • Small molecule regulators of autophagy identified by an image-based high-throughput screen. Abstract Text:

    lihong zhangLihong Zhang,jia yuJia Yu,heling panHeling Pan,ping huPing Hu,yan haoYan Hao,wenqing caiWenqing Cai,hong zhuHong Zhu,albert d yuAlbert D Yu,xin xieXin Xie,dawei maDawei Ma,junying yuanJunying Yuan,lihong zhangLihong Zhang,jia yuJia Yu,heling panHeling Pan,ping huPing Hu,yan haoYan Hao,wenqing caiWenqing Cai,hong zhuHong Zhu,albert d yuAlbert D Yu,xin xieXin Xie,dawei maDawei Ma,junying yuanJunying Yuan,

    Autophagy is a lysosome-dependent cellular catabolic mechanism mediating the turnover of intracellular organelles and long-lived proteins. Reduction of autophagy activity has been shown to lead to the accumulation of misfolded proteins in neurons and may be involved in chronic neurodegenerative diseases such as Huntington's disease and Alzheimer's disease. To explore the mechanism of autophagy and identify small molecules that can activate it, we developed a series of high-throughput image-based screens for small-molecule regulators of autophagy. This series of screens allowed us to distinguish compounds that can truly induce autophagic degradation from those that induce the accumulation of autophagosomes as a result of causing cellular damage or blocking downstream lysosomal functions. Our analyses led to the identification of eight compounds that can induce autophagy and promote long-lived protein degradation. Interestingly, seven of eight compounds are FDA-approved drugs for treatment of human diseases. Furthermore, we show that these compounds can reduce the levels of expanded polyglutamine repeats in cultured cells. Our studies suggest the possibility that some of these drugs may be useful for the treatment of Huntington's and other human diseases associated with the accumulation of misfolded proteins.

    Small molecule regulators of autophagy identified by an image-based high-throughput screen. Publishing Authors By Initials

    l zhangL Zhang,j yuJ Yu,h panH Pan,p huP Hu,y haoY Hao,w caiW Cai,h zhuH Zhu,ad yuAD Yu,x xieX Xie,d maD Ma,j yuanJ Yuan,l zhangL Zhang,j yuJ Yu,h panH Pan,p huP Hu,y haoY Hao,w caiW Cai,h zhuH Zhu,ad yuAD Yu,x xieX Xie,d maD Ma,j yuanJ Yuan,

    For similar abstracts research abstracts see: abstracts research

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    Small molecule regulators of autophagy identified by an image-based high-throughput screen. Journal Published:

    PUBLICATION TYPE: Research Support, Non-U.S. Gov

    Journal: Proceedings of the National Academy of Sciences of

    VOLUME: 104

    Page Numbers: 19023-8

    Journal Abbreviation: Proc. Natl. Acad. Sci. U.S.A.

    ISSN: 1091-6490

    DAY: 16

    MONTH: 11

    YEAR: 2007

    Small molecule regulators of autophagy identified by an image-based high-throughput screen. Information

    Number of References:

    LANGUAGE: eng

    NlmUniqueID: 7505876

    Small molecule regulators of autophagy identified by an image-based high-throughput screen. Keywords Mesh Terms:

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    Grant and Affiliation Information for Small molecule regulators of autophagy identified by an image-based high-throughput screen.

    AFFILIATION: State Key Laboratory of Bioorganic and Natural Products Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 354 Fenglin Road, Shanghai 200032, China.

    Country: United States

    United States Research PublicationUnited States Research Publication

    AGENCY: United States NIA

    GRANT: R37 AG12859

    ACRONYM: AG

    MEDLINETA: Proc Natl Acad Sci U S A

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