Onjisaponin B Derived from Radix Polygalae Enhances Autophagy and Accelerates the Degradation of Mutant α-Synuclein and Huntingtin in PC-12 Cells
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 tha...
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doaj-817de591875a49ab982d92df9fe960f72020-11-25T00:24:04ZengMDPI AGInternational Journal of Molecular Sciences1422-00672013-11-011411226182264110.3390/ijms141122618Onjisaponin B Derived from Radix Polygalae Enhances Autophagy and Accelerates the Degradation of Mutant α-Synuclein and Huntingtin in PC-12 CellsAn-Guo WuVincent Kam-Wai WongSu-Wei XuWai-Kit ChanChoi-In NgLiang LiuBetty Yuen-Kwan LawEmerging 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.http://www.mdpi.com/1422-0067/14/11/22618autophagyRadix Polygalaeonjisaponin BAMPKmTORα-synucleinhuntingtinPC-12 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
An-Guo Wu Vincent Kam-Wai Wong Su-Wei Xu Wai-Kit Chan Choi-In Ng Liang Liu Betty Yuen-Kwan Law |
spellingShingle |
An-Guo Wu Vincent Kam-Wai Wong Su-Wei Xu Wai-Kit Chan Choi-In Ng Liang Liu Betty Yuen-Kwan Law Onjisaponin B Derived from Radix Polygalae Enhances Autophagy and Accelerates the Degradation of Mutant α-Synuclein and Huntingtin in PC-12 Cells International Journal of Molecular Sciences autophagy Radix Polygalae onjisaponin B AMPK mTOR α-synuclein huntingtin PC-12 |
author_facet |
An-Guo Wu Vincent Kam-Wai Wong Su-Wei Xu Wai-Kit Chan Choi-In Ng Liang Liu Betty Yuen-Kwan Law |
author_sort |
An-Guo Wu |
title |
Onjisaponin B Derived from Radix Polygalae Enhances Autophagy and Accelerates the Degradation of Mutant α-Synuclein and Huntingtin in PC-12 Cells |
title_short |
Onjisaponin B Derived from Radix Polygalae Enhances Autophagy and Accelerates the Degradation of Mutant α-Synuclein and Huntingtin in PC-12 Cells |
title_full |
Onjisaponin B Derived from Radix Polygalae Enhances Autophagy and Accelerates the Degradation of Mutant α-Synuclein and Huntingtin in PC-12 Cells |
title_fullStr |
Onjisaponin B Derived from Radix Polygalae Enhances Autophagy and Accelerates the Degradation of Mutant α-Synuclein and Huntingtin in PC-12 Cells |
title_full_unstemmed |
Onjisaponin B Derived from Radix Polygalae Enhances Autophagy and Accelerates the Degradation of Mutant α-Synuclein and Huntingtin in PC-12 Cells |
title_sort |
onjisaponin b derived from radix polygalae enhances autophagy and accelerates the degradation of mutant α-synuclein and huntingtin in pc-12 cells |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1422-0067 |
publishDate |
2013-11-01 |
description |
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. |
topic |
autophagy Radix Polygalae onjisaponin B AMPK mTOR α-synuclein huntingtin PC-12 |
url |
http://www.mdpi.com/1422-0067/14/11/22618 |
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