UM
A novel curcumin analog binds to and activates TFEB in vitro and in vivo independent of MTOR inhibition
Song J.-X.1; Sun Y.-R.3; Peluso I.2; Zeng Y.1; Yu X.1; Lu J.-H.5; Xu Z.3; Wang M.-Z.1; Liu L.-F.1; Huang Y.-Y.1; Chen L.-L.1; Durairajan S.S.K.1; Zhang H.-J.1; Zhou B.4; Zhang H.-Q.1; Lu A.1; Ballabio A.2; Medina D.L.2; Guo Z.3; Li M.1
2016-08-02
Source PublicationAutophagy
ISSN15548635 15548627
Volume12Issue:8Pages:1372-1389
AbstractAutophagy dysfunction is a common feature in neurodegenerative disorders characterized by accumulation of toxic protein aggregates. Increasing evidence has demonstrated that activation of TFEB (transcription factor EB), a master regulator of autophagy and lysosomal biogenesis, can ameliorate neurotoxicity and rescue neurodegeneration in animal models. Currently known TFEB activators are mainly inhibitors of MTOR (mechanistic target of rapamycin [serine/threonine kinase]), which, as a master regulator of cell growth and metabolism, is involved in a wide range of biological functions. Thus, the identification of TFEB modulators acting without inhibiting the MTOR pathway would be preferred and probably less deleterious to cells. In this study, a synthesized curcumin derivative termed C1 is identified as a novel MTOR-independent activator of TFEB. Compound C1 specifically binds to TFEB at the N terminus and promotes TFEB nuclear translocation without inhibiting MTOR activity. By activating TFEB, C1 enhances autophagy and lysosome biogenesis in vitro and in vivo. Collectively, compound C1 is an orally effective activator of TFEB and is a potential therapeutic agent for the treatment of neurodegenerative diseases.
Keywordautophagy curcumin analogs lysosomal biogenesis mechanistic target of rapamycin transcription factor EB
DOI10.1080/15548627.2016.1179404
URLView the original
Language英語
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Cited Times [WOS]:30   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionUniversity of Macau
Affiliation1.Hong Kong Baptist University
2.TIGEM Telethon Institute of Genetics and Medicine
3.Hong Kong University of Science and Technology
4.State Key Laboratory of Applied Organic Chemistry
5.Universidade de Macau
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GB/T 7714
Song J.-X.,Sun Y.-R.,Peluso I.,et al. A novel curcumin analog binds to and activates TFEB in vitro and in vivo independent of MTOR inhibition[J]. Autophagy,2016,12(8):1372-1389.
APA Song J.-X..,Sun Y.-R..,Peluso I..,Zeng Y..,Yu X..,...&Li M..(2016).A novel curcumin analog binds to and activates TFEB in vitro and in vivo independent of MTOR inhibition.Autophagy,12(8),1372-1389.
MLA Song J.-X.,et al."A novel curcumin analog binds to and activates TFEB in vitro and in vivo independent of MTOR inhibition".Autophagy 12.8(2016):1372-1389.
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