Tetramethylpyrazine Analogue T-006 Exerts Neuroprotective Effects against 6-Hydroxydopamine-Induced Parkinson's Disease In Vitro and In Vivo

Zhou, Hefeng1; Shao, Min1; Yang, Xuanjun2; Li, Chuwen4; Cui, Guozhen1; Gao, Cheng2; Di, Lijun5; Zhong, Hanbing3; Wang, Yuqiang6; Zhang, Zaijun6; Lee, Simon Ming-Yuen2

2019

10.1155/2019/8169125

Oxidative Medicine and Cellular Longevity   影响因子和分区

19420994

1942-0994

Parkinson's disease (PD) is a neurodegenerative disorder characterized by the progressive loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc), and there is no cure for it at present. We have previously reported that the tetramethylpyrazine (TMP) derivative T-006 exhibited beneficial effects in Alzheimer's disease (AD) models. However, its effect on PD remains unclear. In the present study, we investigated the neuroprotective effects and underlying mechanisms of T-006 against 6-hydroxydopamine- (6-OHDA-) induced lesions in in vivo and in vitro PD models. Our results demonstrated that T-006 alleviated mitochondrial membrane potential loss and restored the energy metabolism and mitochondrial biogenesis that were induced by 6-OHDA in PC12 cells. In addition, animal experiments showed that administration of T-006 significantly attenuated the 6-OHDA-induced loss of tyrosine hydroxylase- (TH-) positive neurons in the SNpc, as well as dopaminergic nerve fibers in the striatum, and also increased the concentration of dopamine and its metabolites (DOPAC, HVA) in the striatum. Functional deficits were restored following T-006 treatment in 6-OHDA-lesioned mice, as demonstrated by improved motor coordination and rotational behavior. In addition, we found that the neuroprotective effects of T-006 were mediated, at least in part, by the activation of both the PKA/Akt/GSK-3β and CREB/PGC-1α/NRF-1/TFAM pathways. In summary, our findings demonstrate that T-006 could be developed as a novel neuroprotective agent for PD, and the two pathways might be promising therapeutic targets for PD.
© 2019 Hefeng Zhou et al.

SCI ; EI

英语

其他

[MYRG2016-00129-ICMS-QRCM MYRG139] ; [062-2017-AIR 134/2014/A3 069/2015/A2]

Cell Biology

Cell Biology

WOS:000501023700005

Hindawi Limited, 410 Park Avenue, 15th Floor, 287 pmb, New York, NY 10022, United States

20194907778287

Amines ; Amino acids ; Mammals ; Metabolism ; Metabolites ; Mitochondria ; Neurons ; Restoration

Bioengineering and Biology:461 ; Organic Compounds:804.1

Web of Science

1.Department of Bioengineering, Zhuhai Campus of Zunyi Medical University, Zhuha, China
2.State Key Laboratory of Quality Research in Chinese Medicine and Institute of Chinese Medical Sciences, University of Macau, China
3.Department of Biology, South University of Science and Technology, Shenzhen, China
4.Key Laboratory of Molecular Target and Clinical Pharmacology, School of Pharmaceutical Sciences, Guangzhou Medical University, Guangzhou, China
5.Cancer Center, Faculty of Health Sciences, University of Macau, China
6.Institute of New Drug Research, College of Pharmacy, Jinan University, Guangzhou, China

Zhou, Hefeng,Shao, Min,Yang, Xuanjun,et al. Tetramethylpyrazine Analogue T-006 Exerts Neuroprotective Effects against 6-Hydroxydopamine-Induced Parkinson's Disease In Vitro and In Vivo[J]. Oxidative Medicine and Cellular Longevity,2019,2019.

Zhou, Hefeng.,Shao, Min.,Yang, Xuanjun.,Li, Chuwen.,Cui, Guozhen.,...&Lee, Simon Ming-Yuen.(2019).Tetramethylpyrazine Analogue T-006 Exerts Neuroprotective Effects against 6-Hydroxydopamine-Induced Parkinson's Disease In Vitro and In Vivo.Oxidative Medicine and Cellular Longevity,2019.

Zhou, Hefeng,et al."Tetramethylpyrazine Analogue T-006 Exerts Neuroprotective Effects against 6-Hydroxydopamine-Induced Parkinson's Disease In Vitro and In Vivo".Oxidative Medicine and Cellular Longevity 2019(2019).