Isorhynchophylline, a natural alkaloid, promotes the degradation of a-synuclein in neuronal cells via inducing autophagy

Jia-Hong Lu, Jie-Qiong Tan, Siva Durairajan, liang-feng liu, Zhuohua Zhang, Long Ma, Han-Ming Shen, Edwin Chan, Min Li

    Research output: Contribution to journalArticle

    96 Citations (Scopus)

    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.

    Original languageEnglish
    Pages (from-to)98-108
    Number of pages11
    JournalAutophagy
    Volume8
    Issue number1
    DOIs
    Publication statusPublished - 2012

    Fingerprint Dive into the research topics of 'Isorhynchophylline, a natural alkaloid, promotes the degradation of a-synuclein in neuronal cells via inducing autophagy'. Together they form a unique fingerprint.

  • Cite this

    Lu, J-H., Tan, J-Q., Durairajan, S., liu, L., Zhang, Z., Ma, L., Shen, H-M., Chan, E., & Li, M. (2012). Isorhynchophylline, a natural alkaloid, promotes the degradation of a-synuclein in neuronal cells via inducing autophagy. Autophagy, 8(1), 98-108. https://doi.org/10.4161/auto.8.1.18313