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Corynoxine, a natural autophagy enhancer, promotes the clearance of alpha-synuclein via Akt/mTOR pathway
Chen L.-L.2; Song J.-X.2; Lu J.-H.2; Yuan Z.-W.2; Liu L.-F.2; Durairajan S.S.K.2; Li M.2
2014
Source PublicationJournal of Neuroimmune Pharmacology
ISSN15571904 15571890
Volume9Issue:3Pages:380-387
AbstractParkinson's disease (PD) is the second most common neurodegenerative disorder characterized by the accumulation of protein aggregates (namely Lewy bodies) in dopaminergic neurons in the substantia nigra region of the brain. Alpha-synuclein (α-syn) is the major component of Lewy bodies in PD patients, and impairment of the autophagy-lysosomal system has been linked to its accumulation. In our previous study, we identified an oxindole alkaloid Corynoxine B (Cory B), isolated from Uncaria rhynchophylla (Miq.) Jacks (Gouteng in Chinese), as a Beclin-1-dependent autophagy inducer. In this work, we show that Cory, an enantiomer of Cory B, also induces autophagy in different neuronal cell lines, including N2a and SHSY-5Y cells, which is paralleled with increased lysosomal enzyme cathepsin D. In vivo, Cory promotes the formation of autophagosomes in the fat bodies of Drosophila. By inducing autophagy, Cory promotes the clearance of wild-type and A53T α-syn in inducible PC12 cells. Interestingly, different from its enantiomer Cory B, Cory induces autophagy through the Akt/mTOR pathway as evidenced by the reduction in the levels of phospho-Akt, phospho-mTOR and phospho-p70 S6 Kinase. Collectively, our findings provide experimental evidence for developing Cory as a new autophagy enhancer from Chinese herbal medicine, which may have potential application in the prevention or treatment of PD. © 2014 Springer Science+Business Media.
KeywordAlpha-synuclein autophagy Corynoxine mTOR Parkinson's disease
DOI10.1007/s11481-014-9528-2
URLView the original
Language英語
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Cited Times [WOS]:39   [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
Chen L.-L.,Song J.-X.,Lu J.-H.,et al. Corynoxine, a natural autophagy enhancer, promotes the clearance of alpha-synuclein via Akt/mTOR pathway[J]. Journal of Neuroimmune Pharmacology,2014,9(3):380-387.
APA Chen L.-L..,Song J.-X..,Lu J.-H..,Yuan Z.-W..,Liu L.-F..,...&Li M..(2014).Corynoxine, a natural autophagy enhancer, promotes the clearance of alpha-synuclein via Akt/mTOR pathway.Journal of Neuroimmune Pharmacology,9(3),380-387.
MLA Chen L.-L.,et al."Corynoxine, a natural autophagy enhancer, promotes the clearance of alpha-synuclein via Akt/mTOR pathway".Journal of Neuroimmune Pharmacology 9.3(2014):380-387.
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