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Isorhynchophylline, a natural alkaloid, promotes the degradation of α-synuclein in neuronal cells via inducing autophagy
Lu J.-H.4; Tan J.-Q.2; Durairajan S.S.K.4; Liu L.-F.4; Zhang Z.-H.2; Ma L.2; Shen H.-M.1; Chan E.3; Li M.4
2012
Source PublicationAutophagy
ISSN15548635 15548627
Volume8Issue:1Pages:98-108
AbstractAccumulation of α-synuclein (α-syn) in the brain is a pathogenic feature and also a causative factor of Parkinson disease. Isorhynchophylline (IsoRhy) is a major tetracyclic oxindole alkaloid isolated from the Chinese herbal medicine Uncaria rhynchophylla (Miq.)Jacks (Gouteng in Chinese), which has been used for the treatment of neurological diseases in East Asia for centuries. Here we report a novel function of IsoRhy as a neuronal autophagy inducer. IsoRhy induced autophagy in different neuronal cell lines, including N2a, SH-SY5Y and PC12 cells, and also in primary cortical neurons. Furthermore, IsoRhy induced autophagy in the fat bodies of Drosophila. IsoRhy promoted clearance of wild-type, A53T and A30P α-syn monomers, α-syn oligomers and α-syn/synphilin-1 aggresomes in neuronal cells via the autophagy-lysosome pathway. More importantly, IsoRhy was able to decrease the expression levels of wild-type and A53T α-syn protein in differentiated human dopaminergic neurons. Notably, IsoRhy-induced autophagy was independent of the mTOR pathway but dependent on the function of Beclin 1. Taken together, data from this study raise the possibility that oxindole alkaloid derivatives may serve as a means to stimulate autophagy in neuronal cells, thereby exerting preventive and therapeutic values against neurodegenerative diseases such as Parkinson disease by reducing pathogenic protein aggregates in neurons. © 2012 Landes Bioscience.
KeywordAlpha-synuclein Autophagy Isorhynchophylline Neuron Oligomers Parkinson disease Protein aggregates
DOI10.4161/auto.8.1.18313
URLView the original
Language英語
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Cited Times [WOS]:79   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
Affiliation1.Yong Loo Lin School of Medicine
2.Central South University China
3.Chinese University of Hong Kong
4.Hong Kong Baptist University
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GB/T 7714
Lu J.-H.,Tan J.-Q.,Durairajan S.S.K.,et al. Isorhynchophylline, a natural alkaloid, promotes the degradation of α-synuclein in neuronal cells via inducing autophagy[J]. Autophagy,2012,8(1):98-108.
APA Lu J.-H..,Tan J.-Q..,Durairajan S.S.K..,Liu L.-F..,Zhang Z.-H..,...&Li M..(2012).Isorhynchophylline, a natural alkaloid, promotes the degradation of α-synuclein in neuronal cells via inducing autophagy.Autophagy,8(1),98-108.
MLA Lu J.-H.,et al."Isorhynchophylline, a natural alkaloid, promotes the degradation of α-synuclein in neuronal cells via inducing autophagy".Autophagy 8.1(2012):98-108.
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