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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...

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Autores principales: 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
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
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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.
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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
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