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HMGB1 is involved in autophagy inhibition caused by SNCA/a-synuclein overexpression :A process modulated by the natural autophagy inducer corynoxine B
Song J.-X.2; Lu J.-H.2; Liu L.-F.2; Chen L.-L.2; Durairajan S.S.K.2; Yue Z.1; Zhang H.-Q.2; Li M.2
2014
Source PublicationAutophagy
ISSN15548627 15548635
Volume10Issue:1Pages:144-154
AbstractSNC A/a-synuclein and its rare mutations are considered as the culprit proteins in Parkinson disease (PD). Wild-type (WT) SNC A has been shown to impair macroautophagy in mammalian cells and in transgenic mice. In this study, we monitored the dynamic changes in autophagy process and confirmed that overexpression of both WT and SNC AA53T inhibits autophagy in PC12 cells in a time-dependent manner. Furthermore, we showed that SNC A binds to both cytosolic and nuclear high mobility group box 1 (HMGB1), impairs the cytosolic translocation of HMGB1, blocks HMGB1- BECN 1 binding, and strengthens BECN 1-BCL2 binding. Deregulation of these molecular events by SNC A overexpression leads to autophagy inhibition. Overexpression of BECN 1 restores autophagy and promotes the clearance of SNC A. siRN A knockdown of Hmgb1 inhibits basal autophagy and abolishes the inhibitory effect of SNC A on autophagy while overexpression of HMGB1 restores autophagy. Corynoxine B, a natural autophagy inducer, restores the deficient cytosolic translocation of HMGB1 and autophagy in cells overexpressing SNC A, which may be attributed to its ability to block SNC A-HMGB1 interaction. Based on these findings, we propose that SNC A-induced impairment of autophagy occurs, in part, through HMGB1, which may provide a potential therapeutic target for PD.© 2014 Landes Bioscience.
KeywordAutophagy Corynoxine B HMGB1 Parkinson disease SNCA
DOI10.4161/auto.26751
URLView the original
Language英語
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Cited Times [WOS]:66   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
Affiliation1.Icahn School of Medicine at Mount Sinai
2.Hong Kong Baptist University
Recommended Citation
GB/T 7714
Song J.-X.,Lu J.-H.,Liu L.-F.,et al. HMGB1 is involved in autophagy inhibition caused by SNCA/a-synuclein overexpression :A process modulated by the natural autophagy inducer corynoxine B[J]. Autophagy,2014,10(1):144-154.
APA Song J.-X..,Lu J.-H..,Liu L.-F..,Chen L.-L..,Durairajan S.S.K..,...&Li M..(2014).HMGB1 is involved in autophagy inhibition caused by SNCA/a-synuclein overexpression :A process modulated by the natural autophagy inducer corynoxine B.Autophagy,10(1),144-154.
MLA Song J.-X.,et al."HMGB1 is involved in autophagy inhibition caused by SNCA/a-synuclein overexpression :A process modulated by the natural autophagy inducer corynoxine B".Autophagy 10.1(2014):144-154.
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