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

Shao Ping Wu, Ai Ling Fu, Yu Xia Wang, Lei Ping Yu, Pei Yuan Jia, Qian Li, Guo Zhang Jin, Man Ji Sun

Research output: Contribution to journalArticlepeer-review

34 Scopus citations

Abstract

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 μM) 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.

Original languageEnglish (US)
Pages (from-to)1-6
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume346
Issue number1
DOIs
StatePublished - Jul 21 2006

Keywords

  • 6-Hydroxydopamine
  • Parkinson's disease
  • Protein transduction domain
  • Tyrosine hydroxylase

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