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Down-regulation of α-synuclein expression can rescue dopaminergic cells from cell death in the substantia nigra of Parkinson’s disease rat model

Authors
Journal
Biochemical and Biophysical Research Communications
0006-291X
Publisher
Elsevier
Publication Date
Volume
341
Issue
4
Identifiers
DOI: 10.1016/j.bbrc.2006.01.057
Keywords
  • Parkinson’S Disease
  • α-Synuclein
  • Mpp+Intoxication
  • Aav
  • Ribozymes
  • Substantia Nigra
Disciplines
  • Biology
  • Design
  • Medicine

Abstract

Abstract Fibrillization and aggregation of α-synuclein may play a critical role in neurodegenerative diseases like Parkinson’s diseases. Adeno-associated virus (AAV) vector delivery of an α-synuclein ribozyme was tested for its silencing effect on degenerating nigrostriatal neurons in the MPP + model of Parkinson’s disease. We designed α-synuclein ribozyme against human α-synuclein gene expression and constructed α-synuclein ribozymes-carrying rAAV vector (designated rAAV-SynRz). Co-transfection of rAAV-SynRz and rAAV-α-synuclein into HEK293 cells resulted in down-regulation of α-synuclein protein expression in vitro. Then, rAAV-SynRz was injected into the substantia nigra (SN) of MPP +-treated rats. Cell counts of TH-positive neurons in the SN revealed that rAAV-SynRz significantly protected TH-positive cells against apoptotic death, compared with those of rAAV-EGFP or no rAAV injected rats. Our results indicate that the use of rAAV-SynRz allowed the survival of higher number of TH-positive neurons in SN in the MPP + model. Down-regulation of α-synuclein expression could be potentially a suitable target for gene therapy of Parkinson’s disease.

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