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Auraptene Mitigates Parkinson's Disease-Like Behavior by Protecting Inhibition of Mitochondrial Respiration and Scavenging Reactive Oxygen Species.
Int J Mol Sci. 2019 Jul 11; 20(14)IJ

Abstract

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.

Authors+Show Affiliations

Department of Biochemistry, Chungnam National University School of Medicine, Daejeon 35015, Korea. Department of Medical Science, Chungnam National University School of Medicine, Daejeon 35015, Korea. Infection Control Convergence Research Center, Chungnam National University School of Medicine, Daejeon 35015, Korea.Department of Biochemistry, Chungnam National University School of Medicine, Daejeon 35015, Korea. Infection Control Convergence Research Center, Chungnam National University School of Medicine, Daejeon 35015, Korea.Department of Biochemistry, Chungnam National University School of Medicine, Daejeon 35015, Korea. Department of Medical Science, Chungnam National University School of Medicine, Daejeon 35015, Korea. Infection Control Convergence Research Center, Chungnam National University School of Medicine, Daejeon 35015, Korea.Department of Biochemistry, Chungnam National University School of Medicine, Daejeon 35015, Korea. Infection Control Convergence Research Center, Chungnam National University School of Medicine, Daejeon 35015, Korea.Department of Biochemistry, Chungnam National University School of Medicine, Daejeon 35015, Korea. Infection Control Convergence Research Center, Chungnam National University School of Medicine, Daejeon 35015, Korea.Department of Biochemistry, Chungnam National University School of Medicine, Daejeon 35015, Korea. Department of Medical Science, Chungnam National University School of Medicine, Daejeon 35015, Korea. Infection Control Convergence Research Center, Chungnam National University School of Medicine, Daejeon 35015, Korea.Department of Biochemistry, Chungnam National University School of Medicine, Daejeon 35015, Korea. Department of Medical Science, Chungnam National University School of Medicine, Daejeon 35015, Korea. Infection Control Convergence Research Center, Chungnam National University School of Medicine, Daejeon 35015, Korea.Department of Biochemistry, Chungnam National University School of Medicine, Daejeon 35015, Korea. Department of Medical Science, Chungnam National University School of Medicine, Daejeon 35015, Korea. Infection Control Convergence Research Center, Chungnam National University School of Medicine, Daejeon 35015, Korea.Department of Biochemistry, Chungnam National University School of Medicine, Daejeon 35015, Korea. Research Institute for Medical Science, Chungnam National University School of Medicine, Daejeon 35015, Korea.Department of Biochemistry, Chungnam National University School of Medicine, Daejeon 35015, Korea. Department of Neurology, Chungnam National University Hospital, Daejeon 35015, Korea.Department of Biochemistry, Chungnam National University School of Medicine, Daejeon 35015, Korea. Department of Pathology, Chungnam National University School of Medicine, Daejeon 35015, Korea.Department of Medical Science, Chungnam National University School of Medicine, Daejeon 35015, Korea. Department of Anesthesiology and pain medicine, Chungnam National University Hospital, Daejeon 35015, Korea. Department of Anesthesiology and pain medicine, Chungnam National University, Daejeon 35015, Korea. Brain Research Institute, Chungnam National University School of Medicine, Daejeon 35015, Korea.Department of Biochemistry, Chungnam National University School of Medicine, Daejeon 35015, Korea. mitochondria@cnu.ac.kr. Department of Medical Science, Chungnam National University School of Medicine, Daejeon 35015, Korea. mitochondria@cnu.ac.kr. Research Institute for Medical Science, Chungnam National University School of Medicine, Daejeon 35015, Korea. mitochondria@cnu.ac.kr.Department of Biochemistry, Chungnam National University School of Medicine, Daejeon 35015, Korea. junyoung3@gmail.com. Department of Medical Science, Chungnam National University School of Medicine, Daejeon 35015, Korea. junyoung3@gmail.com. Infection Control Convergence Research Center, Chungnam National University School of Medicine, Daejeon 35015, Korea. junyoung3@gmail.com.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31336718

Citation

Jang, Yunseon, et al. "Auraptene Mitigates Parkinson's Disease-Like Behavior By Protecting Inhibition of Mitochondrial Respiration and Scavenging Reactive Oxygen Species." International Journal of Molecular Sciences, vol. 20, no. 14, 2019.
Jang Y, Choo H, Lee MJ, et al. Auraptene Mitigates Parkinson's Disease-Like Behavior by Protecting Inhibition of Mitochondrial Respiration and Scavenging Reactive Oxygen Species. Int J Mol Sci. 2019;20(14).
Jang, Y., Choo, H., Lee, M. J., Han, J., Kim, S. J., Ju, X., Cui, J., Lee, Y. L., Ryu, M. J., Oh, E. S., Choi, S. Y., Chung, W., Kweon, G. R., & Heo, J. Y. (2019). Auraptene Mitigates Parkinson's Disease-Like Behavior by Protecting Inhibition of Mitochondrial Respiration and Scavenging Reactive Oxygen Species. International Journal of Molecular Sciences, 20(14). https://doi.org/10.3390/ijms20143409
Jang Y, et al. Auraptene Mitigates Parkinson's Disease-Like Behavior By Protecting Inhibition of Mitochondrial Respiration and Scavenging Reactive Oxygen Species. Int J Mol Sci. 2019 Jul 11;20(14) PubMed PMID: 31336718.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Auraptene Mitigates Parkinson's Disease-Like Behavior by Protecting Inhibition of Mitochondrial Respiration and Scavenging Reactive Oxygen Species. AU - Jang,Yunseon, AU - Choo,Hyosun, AU - Lee,Min Joung, AU - Han,Jeongsu, AU - Kim,Soo Jeong, AU - Ju,Xianshu, AU - Cui,Jianchen, AU - Lee,Yu Lim, AU - Ryu,Min Jeong, AU - Oh,Eung Seok, AU - Choi,Song-Yi, AU - Chung,Woosuk, AU - Kweon,Gi Ryang, AU - Heo,Jun Young, Y1 - 2019/07/11/ PY - 2019/06/17/received PY - 2019/07/06/revised PY - 2019/07/09/accepted PY - 2019/7/25/entrez PY - 2019/7/25/pubmed PY - 2019/12/24/medline KW - Parkinson’s disease KW - antioxidant KW - auraptene KW - dopamine neuron KW - mitochondria KW - neuroprotection JF - International journal of molecular sciences JO - Int J Mol Sci VL - 20 IS - 14 N2 - 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. SN - 1422-0067 UR - https://www.unboundmedicine.com/medline/citation/31336718/Auraptene_Mitigates_Parkinson's_Disease_Like_Behavior_by_Protecting_Inhibition_of_Mitochondrial_Respiration_and_Scavenging_Reactive_Oxygen_Species_ L2 - https://www.mdpi.com/resolver?pii=ijms20143409 DB - PRIME DP - Unbound Medicine ER -