Cargando…
Auraptene Mitigates Parkinson’s Disease-Like Behavior by Protecting Inhibition of Mitochondrial Respiration and Scavenging Reactive Oxygen Species
Current therapeutics for Parkinson’s disease (PD) are only effective in providing relief of symptoms such as rigidity, tremors and bradykinesia, and do not exert disease-modifying effects by directly modulating mitochondrial function. Here, we investigated auraptene (AUR) as a potent therapeutic rea...
Autores principales: | , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6679046/ https://www.ncbi.nlm.nih.gov/pubmed/31336718 http://dx.doi.org/10.3390/ijms20143409 |
_version_ | 1783441246959697920 |
---|---|
author | Jang, Yunseon Choo, Hyosun Lee, Min Joung Han, Jeongsu Kim, Soo Jeong Ju, Xianshu Cui, Jianchen Lee, Yu Lim Ryu, Min Jeong Oh, Eung Seok Choi, Song-Yi Chung, Woosuk Kweon, Gi Ryang Heo, Jun Young |
author_facet | Jang, Yunseon Choo, Hyosun Lee, Min Joung Han, Jeongsu Kim, Soo Jeong Ju, Xianshu Cui, Jianchen Lee, Yu Lim Ryu, Min Jeong Oh, Eung Seok Choi, Song-Yi Chung, Woosuk Kweon, Gi Ryang Heo, Jun Young |
author_sort | Jang, Yunseon |
collection | PubMed |
description | Current therapeutics for Parkinson’s disease (PD) are only effective in providing relief of symptoms such as rigidity, tremors and bradykinesia, and do not exert disease-modifying effects by directly modulating mitochondrial function. Here, we investigated auraptene (AUR) as a potent therapeutic reagent that specifically protects neurotoxin-induced reduction of mitochondrial respiration and inhibits reactive oxygen species (ROS) generation. Further, we explored the mechanism and potency of AUR in protecting dopaminergic neurons. Treatment with AUR significantly increased the viability of substantia nigra (SN)-derived SN4741 embryonic dopaminergic neuronal cells and reduced rotenone-induced mitochondrial ROS production. By inducing antioxidant enzymes AUR treatment also increased oxygen consumption rate. These results indicate that AUR exerts a protective effect against rotenone-induced mitochondrial oxidative damage. We further assessed AUR effects in vivo, investigating tyrosine hydroxylase (TH) expression in the striatum and substantia nigra of MPTP-induced PD model mice and behavioral changes after injection of AUR. AUR treatment improved movement, consistent with the observed increase in the number of dopaminergic neurons in the substantia nigra. These results demonstrate that AUR targets dual pathogenic mechanisms, enhancing mitochondrial respiration and attenuating ROS production, suggesting that the preventative potential of this natural compound could lead to improvement in PD-related neurobiological changes. |
format | Online Article Text |
id | pubmed-6679046 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-66790462019-08-19 Auraptene Mitigates Parkinson’s Disease-Like Behavior by Protecting Inhibition of Mitochondrial Respiration and Scavenging Reactive Oxygen Species Jang, Yunseon Choo, Hyosun Lee, Min Joung Han, Jeongsu Kim, Soo Jeong Ju, Xianshu Cui, Jianchen Lee, Yu Lim Ryu, Min Jeong Oh, Eung Seok Choi, Song-Yi Chung, Woosuk Kweon, Gi Ryang Heo, Jun Young Int J Mol Sci Article Current therapeutics for Parkinson’s disease (PD) are only effective in providing relief of symptoms such as rigidity, tremors and bradykinesia, and do not exert disease-modifying effects by directly modulating mitochondrial function. Here, we investigated auraptene (AUR) as a potent therapeutic reagent that specifically protects neurotoxin-induced reduction of mitochondrial respiration and inhibits reactive oxygen species (ROS) generation. Further, we explored the mechanism and potency of AUR in protecting dopaminergic neurons. Treatment with AUR significantly increased the viability of substantia nigra (SN)-derived SN4741 embryonic dopaminergic neuronal cells and reduced rotenone-induced mitochondrial ROS production. By inducing antioxidant enzymes AUR treatment also increased oxygen consumption rate. These results indicate that AUR exerts a protective effect against rotenone-induced mitochondrial oxidative damage. We further assessed AUR effects in vivo, investigating tyrosine hydroxylase (TH) expression in the striatum and substantia nigra of MPTP-induced PD model mice and behavioral changes after injection of AUR. AUR treatment improved movement, consistent with the observed increase in the number of dopaminergic neurons in the substantia nigra. These results demonstrate that AUR targets dual pathogenic mechanisms, enhancing mitochondrial respiration and attenuating ROS production, suggesting that the preventative potential of this natural compound could lead to improvement in PD-related neurobiological changes. MDPI 2019-07-11 /pmc/articles/PMC6679046/ /pubmed/31336718 http://dx.doi.org/10.3390/ijms20143409 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Jang, Yunseon Choo, Hyosun Lee, Min Joung Han, Jeongsu Kim, Soo Jeong Ju, Xianshu Cui, Jianchen Lee, Yu Lim Ryu, Min Jeong Oh, Eung Seok Choi, Song-Yi Chung, Woosuk Kweon, Gi Ryang Heo, Jun Young Auraptene Mitigates Parkinson’s Disease-Like Behavior by Protecting Inhibition of Mitochondrial Respiration and Scavenging Reactive Oxygen Species |
title | Auraptene Mitigates Parkinson’s Disease-Like Behavior by Protecting Inhibition of Mitochondrial Respiration and Scavenging Reactive Oxygen Species |
title_full | Auraptene Mitigates Parkinson’s Disease-Like Behavior by Protecting Inhibition of Mitochondrial Respiration and Scavenging Reactive Oxygen Species |
title_fullStr | Auraptene Mitigates Parkinson’s Disease-Like Behavior by Protecting Inhibition of Mitochondrial Respiration and Scavenging Reactive Oxygen Species |
title_full_unstemmed | Auraptene Mitigates Parkinson’s Disease-Like Behavior by Protecting Inhibition of Mitochondrial Respiration and Scavenging Reactive Oxygen Species |
title_short | Auraptene Mitigates Parkinson’s Disease-Like Behavior by Protecting Inhibition of Mitochondrial Respiration and Scavenging Reactive Oxygen Species |
title_sort | auraptene mitigates parkinson’s disease-like behavior by protecting inhibition of mitochondrial respiration and scavenging reactive oxygen species |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6679046/ https://www.ncbi.nlm.nih.gov/pubmed/31336718 http://dx.doi.org/10.3390/ijms20143409 |
work_keys_str_mv | AT jangyunseon auraptenemitigatesparkinsonsdiseaselikebehaviorbyprotectinginhibitionofmitochondrialrespirationandscavengingreactiveoxygenspecies AT choohyosun auraptenemitigatesparkinsonsdiseaselikebehaviorbyprotectinginhibitionofmitochondrialrespirationandscavengingreactiveoxygenspecies AT leeminjoung auraptenemitigatesparkinsonsdiseaselikebehaviorbyprotectinginhibitionofmitochondrialrespirationandscavengingreactiveoxygenspecies AT hanjeongsu auraptenemitigatesparkinsonsdiseaselikebehaviorbyprotectinginhibitionofmitochondrialrespirationandscavengingreactiveoxygenspecies AT kimsoojeong auraptenemitigatesparkinsonsdiseaselikebehaviorbyprotectinginhibitionofmitochondrialrespirationandscavengingreactiveoxygenspecies AT juxianshu auraptenemitigatesparkinsonsdiseaselikebehaviorbyprotectinginhibitionofmitochondrialrespirationandscavengingreactiveoxygenspecies AT cuijianchen auraptenemitigatesparkinsonsdiseaselikebehaviorbyprotectinginhibitionofmitochondrialrespirationandscavengingreactiveoxygenspecies AT leeyulim auraptenemitigatesparkinsonsdiseaselikebehaviorbyprotectinginhibitionofmitochondrialrespirationandscavengingreactiveoxygenspecies AT ryuminjeong auraptenemitigatesparkinsonsdiseaselikebehaviorbyprotectinginhibitionofmitochondrialrespirationandscavengingreactiveoxygenspecies AT oheungseok auraptenemitigatesparkinsonsdiseaselikebehaviorbyprotectinginhibitionofmitochondrialrespirationandscavengingreactiveoxygenspecies AT choisongyi auraptenemitigatesparkinsonsdiseaselikebehaviorbyprotectinginhibitionofmitochondrialrespirationandscavengingreactiveoxygenspecies AT chungwoosuk auraptenemitigatesparkinsonsdiseaselikebehaviorbyprotectinginhibitionofmitochondrialrespirationandscavengingreactiveoxygenspecies AT kweongiryang auraptenemitigatesparkinsonsdiseaselikebehaviorbyprotectinginhibitionofmitochondrialrespirationandscavengingreactiveoxygenspecies AT heojunyoung auraptenemitigatesparkinsonsdiseaselikebehaviorbyprotectinginhibitionofmitochondrialrespirationandscavengingreactiveoxygenspecies |