BACKGROUND: Synphilin-1 has been shown to be involved in the pathogenesis of Parkinson's disease (PD), and superoxide dismutase (SOD) reduction might induce PD onset. To date, the precise effect of synphilin-1 o...BACKGROUND: Synphilin-1 has been shown to be involved in the pathogenesis of Parkinson's disease (PD), and superoxide dismutase (SOD) reduction might induce PD onset. To date, the precise effect of synphilin-1 on SOD expression remains poorly understood. OBJECTIVE: To explore the influence of synphilin-1 small interfering RNA (siRNA) on SOD expression in a rat model of PD. DESIGN, TIME AND SETTING: A randomized, controlled, animal experiment was performed at the Laboratory of Neurology, Affiliated Hospital of Qingdao University Medical School from June to October 2008. MATERIALS: 6-hydroxydopamine was purchased from Wuhan Boster, China. METHODS: A total of 40 male, Wistar rats were randomly assigned to PD, siRNA, siRNA negative control, and control groups, with 10 rats in each group. Rats from the PD, siRNA, and siRNA negative control groups were injected with 6-hydroxydopamine into the right substantia nigra to establish PD models. In addition, synphilin-1 siRNA and siRNA negative control sequences were separately injected into the right substantia nigra of siRNA, and siRNA negative control groups. The control group rats were treated with a mixture of ascorbic acid and normal saline. MAIN OUTCOME MEASURES: Synphilin-1 and SOD protein and mRNA expression in the substantia nigra was detected by immunohistochemistry and in situ hybridization. RESULTS: Synphilin-1 and SOD protein and mRNA expression were significantly decreased in PD and siRNA negative control groups (P 〈 0.05). However, the siRNA group exhibited opposite effects. CONCLUSION: Synphilin-1 resulted in altered SOD expression, which suggested a protective role for synphilin-1 siRNA in an animal model of PD.展开更多
Parkinson’s disease (PD) is one of the commonest neurodegenerative disorders characterized by the loss of dopaminergic (DAergic) neurons in the substantia nigra and the appearance of Lewy bodies (LBs), whose cytoplas...Parkinson’s disease (PD) is one of the commonest neurodegenerative disorders characterized by the loss of dopaminergic (DAergic) neurons in the substantia nigra and the appearance of Lewy bodies (LBs), whose cytoplasmic inclusions are highly enriched with ubiquitin, synphilin-1, α-synuclein and parkin. Synphilin-1 is an α-synuclein-binding protein and a major component of LBs. It is widely accepted that synphilin-1 is involved in the pathogenic process of PD. This review will provide an overall view of the role of synphilin-1 in the pathogenesis of Parkinson’s disease and the latest findings in this field.展开更多
基金the Young and Middle-Aged Scientists Research Foundation of Shandong Province, No. 200503021
文摘BACKGROUND: Synphilin-1 has been shown to be involved in the pathogenesis of Parkinson's disease (PD), and superoxide dismutase (SOD) reduction might induce PD onset. To date, the precise effect of synphilin-1 on SOD expression remains poorly understood. OBJECTIVE: To explore the influence of synphilin-1 small interfering RNA (siRNA) on SOD expression in a rat model of PD. DESIGN, TIME AND SETTING: A randomized, controlled, animal experiment was performed at the Laboratory of Neurology, Affiliated Hospital of Qingdao University Medical School from June to October 2008. MATERIALS: 6-hydroxydopamine was purchased from Wuhan Boster, China. METHODS: A total of 40 male, Wistar rats were randomly assigned to PD, siRNA, siRNA negative control, and control groups, with 10 rats in each group. Rats from the PD, siRNA, and siRNA negative control groups were injected with 6-hydroxydopamine into the right substantia nigra to establish PD models. In addition, synphilin-1 siRNA and siRNA negative control sequences were separately injected into the right substantia nigra of siRNA, and siRNA negative control groups. The control group rats were treated with a mixture of ascorbic acid and normal saline. MAIN OUTCOME MEASURES: Synphilin-1 and SOD protein and mRNA expression in the substantia nigra was detected by immunohistochemistry and in situ hybridization. RESULTS: Synphilin-1 and SOD protein and mRNA expression were significantly decreased in PD and siRNA negative control groups (P 〈 0.05). However, the siRNA group exhibited opposite effects. CONCLUSION: Synphilin-1 resulted in altered SOD expression, which suggested a protective role for synphilin-1 siRNA in an animal model of PD.
文摘Parkinson’s disease (PD) is one of the commonest neurodegenerative disorders characterized by the loss of dopaminergic (DAergic) neurons in the substantia nigra and the appearance of Lewy bodies (LBs), whose cytoplasmic inclusions are highly enriched with ubiquitin, synphilin-1, α-synuclein and parkin. Synphilin-1 is an α-synuclein-binding protein and a major component of LBs. It is widely accepted that synphilin-1 is involved in the pathogenic process of PD. This review will provide an overall view of the role of synphilin-1 in the pathogenesis of Parkinson’s disease and the latest findings in this field.