期刊
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
卷 341, 期 4, 页码 1088-1095出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2006.01.057
关键词
Parkinson's disease; alpha-synuclein; MPP+ intoxication; AAV; ribozymes; substantia nigra
Fibrillization and aggregation of alpha-synuclein may play a critical role in neurodegenerative diseases like Parkinson's diseases. Adeno-associated virus (AAV) vector delivery of an alpha-synuclein ribozyme was tested for its silencing effect on degenerating nigrostriatal neurons in the MPP+ model of Parkinson's disease. We designed alpha-synuclein ribozyme against human alpha-synuclein gene expression and constructed alpha-synuclein ribozymes-carrying rAAV vector (designated rAAV-SynRz). Co-transfection of rAAV-SynRz and rAAV-alpha-synuclein into HEK293 cells resulted in down-regulation of alpha-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 alpha-synuclein expression could be potentially a suitable target for gene therapy of Parkinson's disease. (c) 2006 Elsevier Inc. All rights reserved.
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