Abstract |
Emerging evidence indicates important protective roles being played by autophagy in neurodegenerative disorders through clearance of aggregate-prone or mutant proteins. In the current study, we aimed to identify autophagy inducers from Chinese medicinal herbs as a potential neuroprotective agent that enhances the clearance of mutant huntingtin and α- synuclein in PC-12 cells. Through intensive screening using the green fluorescent protein-light chain 3 (GFP-LC3) autophagy detection platform, we found that the ethanol extracts of Radix Polygalae ( Yuan Zhi) were capable of inducing autophagy. Further investigation showed that among three single components derived from Radix Polygalae--i.e., polygalacic acid, senegenin and onjisaponin B-- onjisaponin B was able to induce autophagy and accelerate both the removal of mutant huntingtin and A53T α- synuclein, which are highly associated with Huntington disease and Parkinson disease, respectively. Our study further demonstrated that onjisaponin B induces autophagy via the AMPK-mTOR signaling pathway. Therefore, findings in the current study provide detailed insights into the protective mechanism of a novel autophagy inducer, which is valuable for further investigation as a new candidate agent for modulating neurodegenerative disorders through the reduction of toxicity and clearance of mutant proteins in the cellular level.
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Authors | An-Guo Wu, Vincent Kam-Wai Wong, Su-Wei Xu, Wai-Kit Chan, Choi-In Ng, Liang Liu, Betty Yuen-Kwan Law |
Journal | International journal of molecular sciences
(Int J Mol Sci)
Vol. 14
Issue 11
Pg. 22618-41
(Nov 15 2013)
ISSN: 1422-0067 [Electronic] Switzerland |
PMID | 24248062
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Drugs, Chinese Herbal
- HTT protein, human
- Huntingtin Protein
- Nerve Tissue Proteins
- Saponins
- Triterpenes
- alpha-Synuclein
- onjisaponin B
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Topics |
- Animals
- Autophagy
(drug effects)
- Cell Line
- Drugs, Chinese Herbal
(chemistry)
- Humans
- Huntingtin Protein
- Huntington Disease
(drug therapy, genetics)
- Mutation
- Nerve Tissue Proteins
(chemistry, genetics)
- Neurodegenerative Diseases
(drug therapy, genetics)
- Parkinson Disease
(drug therapy, genetics)
- Proteolysis
(drug effects)
- Rats
- Saponins
(administration & dosage, chemistry)
- Signal Transduction
(drug effects, genetics)
- Triterpenes
(administration & dosage, chemistry)
- alpha-Synuclein
(chemistry, genetics)
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