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

J Neurochem. 2011 Feb;116(3):334-41. doi: 10.1111/j.1471-4159.2010.07112.x. Epub 2010 Dec 22.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / pharmacology
  • Animals
  • Cell Death / drug effects
  • Cell Death / physiology
  • Cell Line, Tumor
  • Cytoprotection / drug effects
  • Cytoprotection / physiology
  • Disease Models, Animal
  • Dopamine / biosynthesis
  • Dopamine / physiology
  • Humans
  • Mice
  • Mice, Knockout
  • Mice, Transgenic
  • Nerve Degeneration / drug therapy
  • Nerve Degeneration / genetics
  • Nerve Degeneration / prevention & control
  • Neuroblastoma / enzymology
  • Neuroblastoma / pathology
  • Neuroblastoma / therapy
  • Neuroprotective Agents / metabolism
  • Neuroprotective Agents / pharmacology*
  • Oncogene Protein v-akt / metabolism
  • Parkinsonian Disorders / drug therapy*
  • Parkinsonian Disorders / genetics
  • Parkinsonian Disorders / metabolism
  • Phosphorylation / drug effects
  • Phosphorylation / physiology
  • Ribonuclease, Pancreatic / metabolism
  • Ribonuclease, Pancreatic / pharmacology*
  • Ribonuclease, Pancreatic / therapeutic use

Substances

  • Neuroprotective Agents
  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
  • Oncogene Protein v-akt
  • angiogenin
  • Ribonuclease, Pancreatic
  • Dopamine