Corynoxine, a Natural Autophagy Enhancer, Promotes the Clearance of Alpha-Synuclein via Akt/mTOR Pathway

Parkinson’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...

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Bibliographic Details
Published in:Journal of neuroimmune pharmacology 2014-06, Vol.9 (3), p.380-387
Main Authors: Chen, Lei-Lei, Song, Ju-Xian, Lu, Jia-Hong, Yuan, Zhen-Wei, Liu, Liang-Feng, Durairajan, Siva Sundara Kumar, Li, Min
Format: Article
Language:English
Subjects:
Alkaloids - pharmacology
alpha-Synuclein - metabolism
Animals
Animals, Genetically Modified
Autophagy
Autophagy - drug effects
Autophagy - physiology
Biomedical and Life Sciences
Biomedicine
Cell Biology
Cell Line, Tumor
Drosophila
Humans
Immunology
Indole Alkaloids
Neurosciences
Original Article
Parkinson's disease
Pharmacology/Toxicology
Protein Transport - drug effects
Protein Transport - physiology
Proto-Oncogene Proteins c-akt - metabolism
TOR Serine-Threonine Kinases - metabolism
Virology
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Summary:Parkinson’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.
ISSN:1557-1890
1557-1904
DOI:10.1007/s11481-014-9528-2