title: A neuroprotective role for angiogenin in models of Parkinson's disease.
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.
authors.affiliation: Department of Neurobiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
authors.forename: Trent U
authors.initials: TU
authors.lastname: Steidinger
authors.forename: David G
authors.initials: DG
authors.lastname: Standaert
authors.forename: Talene A
authors.initials: TA
authors.lastname: Yacoubian
mesh_terms: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology; D000818:Animals; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor; D019610:Cytoprotection / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D004298:Dopamine / Q000096:biosynthesis / Q000502:physiology; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009410:Nerve Degeneration / Q000188:drug therapy / Q000235:genetics / Q000517:prevention & control; D009447:Neuroblastoma / Q000201:enzymology / Q000473:pathology / Q000628:therapy; D018696:Neuroprotective Agents / Q000378:metabolism / Q000494:pharmacology*; D051058:Oncogene Protein v-akt / Q000378:metabolism; D020734:Parkinsonian Disorders / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects / Q000502:physiology; D012259:Ribonuclease, Pancreatic / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D018696:Neuroprotective Agents; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D051058:Oncogene Protein v-akt; C046366:angiogenin; D012259:Ribonuclease, Pancreatic; D004298:Dopamine