title: Corynoxine, a natural autophagy enhancer, promotes the clearance of alpha-synuclein via Akt/mTOR pathway.
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.
authors: School of Chinese Medicine, Hong Kong Baptist University, Kowloon, Hong Kong.
authors: Lei-Lei
authors: LL
authors: Chen
authors: Ju-Xian
authors: JX
authors: Song
authors: Jia-Hong
authors: JH
authors: Lu
authors: Zhen-Wei
authors: ZW
authors: Yuan
authors: Liang-Feng
authors: LF
authors: Liu
authors: Siva Sundara Kumar
authors: SS
authors: Durairajan
authors: Min
authors: M
authors: Li
mesh_terms: D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D030801:Animals, Genetically Modified; D001343:Autophagy / Q000187:drug effects* / Q000502:physiology; D045744:Cell Line, Tumor; D004330:Drosophila; D006801:Humans; D026121:Indole Alkaloids; D021381:Protein Transport / Q000187:drug effects / Q000502:physiology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D051844:alpha-Synuclein / Q000378:metabolism*
chemical_list: D000470:Alkaloids; D026121:Indole Alkaloids; D051844:alpha-Synuclein; C054799:corynoxeine; C546842:MTOR protein, human; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases