کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1941246 | 1050805 | 2006 | 8 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Down-regulation of α-synuclein expression can rescue dopaminergic cells from cell death in the substantia nigra of Parkinson’s disease rat model Down-regulation of α-synuclein expression can rescue dopaminergic cells from cell death in the substantia nigra of Parkinson’s disease rat model](/preview/png/1941246.png)
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.
Journal: Biochemical and Biophysical Research Communications - Volume 341, Issue 4, 24 March 2006, Pages 1088–1095