Please use this identifier to cite or link to this item:
|Title:||Isorhynchophylline, a natural alkaloid, promotes the degradation of α-synuclein in neuronal cells via inducing autophagy|
|Citation:||Lu, J.-H., Tan, J.-Q., Durairajan, S.S.K., Liu, L.-F., Zhang, Z.-H., Ma, L., Shen, H.-M., Chan, E., Li, M. (2012-01). Isorhynchophylline, a natural alkaloid, promotes the degradation of α-synuclein in neuronal cells via inducing autophagy. Autophagy 8 (1) : 98-108. ScholarBank@NUS Repository. https://doi.org/10.4161/auto.8.1.18313|
|Abstract:||Accumulation 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.|
|Appears in Collections:||Staff Publications|
Show full item record
Files in This Item:
There are no files associated with this item.
checked on Jul 14, 2018
WEB OF SCIENCETM
checked on Jun 19, 2018
checked on Jun 29, 2018
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.