Document Type

Journal Article

Department/Unit

School of Chinese Medicine

Title

Corynoxine, a natural autophagy enhancer, promotes the clearance of alpha-synuclein via Akt/mTOR pathway

Language

English

Abstract

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. © 2014 Springer Science+Business Media.

Keywords

Alpha-synuclein, autophagy, Corynoxine, mTOR, Parkinson's disease

Publication Date

2014

Source Publication Title

Journal of Neuroimmune Pharmacology

Volume

9

Issue

3

Start Page

380

End Page

387

Publisher

Springer Verlag

DOI

10.1007/s11481-014-9528-2

Link to Publisher's Edition

http://dx.doi.org/10.1007/s11481-014-9528-2

ISSN (print)

15571890

ISSN (electronic)

15571904

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