期刊
JOURNAL OF NEUROCHEMISTRY
卷 116, 期 3, 页码 334-341出版社
WILEY
DOI: 10.1111/j.1471-4159.2010.07112.x
关键词
1-methyl-4-phenylpyridinium; Akt; alpha-synuclein; angiogenin; neuroprotection; Parkinson's disease
资金
- Parkinson Association of Alabama
- American Parkinson Disease Association
- NIH-NINDS [NS060948]
P>We previously observed marked down-regulation of the mRNA for angiogenin, a potent inducer of neovascularization, in a mouse model of Parkinson's disease (PD) based on over-expression of alpha-synuclein. Angiogenin has also been recently implicated in the pathogenesis of amyotrophic lateral sclerosis. In this study, we confirmed that mouse angiogenin-1 protein is dramatically reduced in this transgenic alpha-synuclein mouse model of PD, and examined the effect of angiogenin in cellular models of PD. We found that endogenous angiogenin is present in two dopamine-producing neuroblastoma cell lines, SH-SY5Y and M17, and that exogenous angiogenin is taken up by these cells and leads to phosphorylation of Akt. Applied angiogenin protects against the cell death induced by the neurotoxins 1-methyl-4-phenylpyridinium and rotenone and reduces the activation of caspase 3. Together our data supports the importance of angiogenin in protecting against dopaminergic neuronal cell death and suggests its potential as a therapy for PD.
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