A novel therapeutic approach to 6-OHDA-induced Parkinson's disease in rats via supplementation of PTD-conjugated tyrosine hydroxylase

doi:10.1016/j.bbrc.2006.03.247

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	A novel therapeutic approach to 6-OHDA-induced Parkinson's disease in rats via supplementation of PTD-conjugated tyrosine hydroxylase
	Wu, Shao Ping ; Fu, Ai Ling ; Wang, Yu Xia ; Yu, Lei Ping ; Jia, Pei Yuan ; Li, Qian ; Jin, Guo Zhang ; Sun, Man Ji
刊名	BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
	2006-07-21
卷号	346 期号:1 页码:1-6
关键词	tyrosine hydroxylase protein transduction domain 6-hydroxydopamine Parkinson's disease
ISSN号	0006-291X
DOI	10.1016/j.bbrc.2006.03.247
文献子类	Article
英文摘要	The present study aimed to evaluate whether the protein transduction domain (PTD)-conjugated human tyrosine hydroxylase (TH) fusion protein was effective on the 6-hydroxydopamine (6-OHDA)-induced Parkinson's disease (PD) model rats. An expression vector pET-PTD-TH harbouring the PTD-TH gene was constructed and transformed to the Escherichia coli BL21 cells for expression. The expressed recombinant PTD-TH with a molecular weight of 61 kD was successfully transduced (1 mu M) into the dopaminergic SH-sy5y human neuroblastoma cells in vitro and visualized by immunohistochemical assay. An in vivo experiment in rats showed that the iv administered PTD-TH protein (8 mg/kg) permeated across the blood-brain barrier, penetrated into the striatum and midbrain, and peaked at 5-8 h after the injection. The behavioral effects of PTD-TH on the apomorphine-induced rotations in the PD model rats ;8 weeks after the 6-OHDA lesion showed that a single bolus of PTD-TH (8 mg/kg) iv injection caused a decrement of 60% of the contralateral turns on day 1 and 40% on days 5-17. The results imply that iv delivery of PTD-TH is therapeutically effective on the 6-OHDA-induced PD in rats, the PTD-mediated human TH treatment opening a promising therapeutic direction in treatment of PD. (c) 2006 Elsevier Inc. All rights reserved.
WOS关键词	PROTEIN TRANSDUCTION ; HIV-1 TAT ; CHOLINE-ACETYLTRANSFERASE ; BASIC DOMAIN ; DELIVERY ; CELLS ; GENE
WOS研究方向	Biochemistry & Molecular Biology ; Biophysics
语种	英语
出版者	ACADEMIC PRESS INC ELSEVIER SCIENCE
WOS记录号	WOS:000238549100001
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/273539]
专题	新药研究国家重点实验室中科院受体结构与功能重点实验室
通讯作者	Sun, Man Ji
作者单位	1.Acad Mil Med Sci, Dept Biochem & Pharmacol, Beijing Inst Pharmacol & Toxicol, Beijing 100850, Peoples R China 2.Beijing Ctr Dis Prevent & Control, Beijing 100013, Peoples R China 3.Chinese Acad Sci, Shanghai Inst Biol Sci, State Key Lab Drug Res, Dept Pharmacol, Shanghai 201203, Peoples R China
推荐引用方式 GB/T 7714	Wu, Shao Ping,Fu, Ai Ling,Wang, Yu Xia,et al. A novel therapeutic approach to 6-OHDA-induced Parkinson's disease in rats via supplementation of PTD-conjugated tyrosine hydroxylase[J]. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS,2006,346(1):1-6.
APA	Wu, Shao Ping.,Fu, Ai Ling.,Wang, Yu Xia.,Yu, Lei Ping.,Jia, Pei Yuan.,...&Sun, Man Ji.(2006).A novel therapeutic approach to 6-OHDA-induced Parkinson's disease in rats via supplementation of PTD-conjugated tyrosine hydroxylase.BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS,346(1),1-6.
MLA	Wu, Shao Ping,et al."A novel therapeutic approach to 6-OHDA-induced Parkinson's disease in rats via supplementation of PTD-conjugated tyrosine hydroxylase".BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 346.1(2006):1-6.