A neuroprotective role for angiogenin in models of Parkinson's disease.

Academic Article

Abstract

  • 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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    Keywords

  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine, Animals, Cell Death, Cell Line, Tumor, Cytoprotection, Disease Models, Animal, Dopamine, Humans, Mice, Mice, Knockout, Mice, Transgenic, Nerve Degeneration, Neuroblastoma, Neuroprotective Agents, Oncogene Protein v-akt, Parkinsonian Disorders, Phosphorylation, Ribonuclease, Pancreatic

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    Author List

  • Steidinger TU; Standaert DG; Yacoubian TA

    • Start Page

  • 334

    • End Page

  • 341

    • Volume

  • 116

    • Issue

  • 3