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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
2019-11-14
Source PublicationOxidative Medicine and Cellular Longevity
ISSN1942-0900
Volume2019
Abstract

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.

DOI10.1155/2019/8169125
URLView the original
Indexed BySCIE
Language英語English
WOS Research AreaCell Biology
WOS SubjectCell Biology
WOS IDWOS:000501023700005
Scopus ID2-s2.0-85075776167
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Cited Times [WOS]:10   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
Corresponding AuthorZhang,Zaijun; Lee,Simon Ming Yuen
Affiliation1.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,Macao
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,Macao
6.Institute of New Drug Research,College of Pharmacy,Jinan University,Guangzhou,China
Corresponding Author AffilicationInstitute of Chinese Medical Sciences
Recommended Citation
GB/T 7714
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.
APA Zhou,Hefeng,Shao,Min,Yang,Xuanjun,Li,Chuwen,Cui,Guozhen,Gao,Cheng,Di,Lijun,Zhong,Hanbing,Wang,Yuqiang,Zhang,Zaijun,&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.
MLA 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).
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