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

by | CIRS, Functional & Integrative Medicine, ISEAI, Neurodegeneration & Brain Health

https://www.tandfonline.com/doi/abs/10.4161/auto.8.1.18313

Comment; Autophagy is the process by which abnormal products of metabolism are “eaten up” and removed before they can cause (more) damage. It’s an essential part of normal homeostasis. Isorhynchophylline promotes the process, clearing abnormal and waste products before problems arise because of them.

Jia-Hong Lu,Jie-Qiong Tan,Siva Sundara Kumar Durairajan,Liang-Feng Liu,Zhuo-Hua Zhang,Long Ma, show allPages 98-108 | Received 26 Jul 2011, Accepted 05 Oct 2011, Published online: 01 Jan 2012

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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.

Dr. Raymond Oenbrink
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