Control of Motoneuron Survival by Angiogenin Journal Articles

abstract

• Mutations in the hypoxia-inducible factor angiogenin (ANG) have been identified in Amyotrophic Lateral Sclerosis (ALS) patients, but the potential role ofANGin ALS pathogenesis was undetermined. Here we show that angiogenin promotes motoneuron survival bothin vitroandin vivo. Angiogenin protected cultured motoneurons against excitotoxic injury in a PI-3-kinase/Akt kinase-dependent manner, whereas knock-down of angiogenin potentiated excitotoxic motoneuron death. Expression of wild-typeANGprotected against endoplasmic reticulum (ER) stress-induced and trophic-factor-withdrawal-induced cell deathin vitro, whereas the ALS-associatedANGmutant K40I exerted no protective activity and failed to activate Akt-1. InSOD1G93Amice angiogenin delivery increased lifespan and motoneuron survival, restored the disease-associated decrease in Akt-1 survival signaling, and reversed a pathophysiological increase in ICAM-1 expression. Our data demonstrate that angiogenin is a key factor in the control of motoneuron survival.

authors

• Kieran, Dairín
• Sebastia, Jordi
• Greenway, Matthew
• King, Matthew A
• Connaughton, Dervla
• Concannon, Caoimhin G
• Fenner, Beau
• Hardiman, Orla
• Prehn, Jochen HM

status

• published 

publication date

• December 24, 2008

has subject area

• 11 Medical and Health Sciences (FoR)
• 17 Psychology and Cognitive Sciences (FoR)
• Amyotrophic Lateral Sclerosis (MeSH)
• Androstadienes (MeSH)
• Animals (MeSH)
• Cell Survival (MeSH)
• Cells, Cultured (MeSH)
• Disease Models, Animal (MeSH)
• Embryo, Mammalian (MeSH)
• Enzyme Inhibitors (MeSH)
• Excitatory Amino Acid Agonists (MeSH)
• Female (MeSH)
• Gene Expression (MeSH)
• Gene Expression Regulation (MeSH)
• Insulin-Like Growth Factor I (MeSH)
• Intercellular Adhesion Molecule-1 (MeSH)
• Male (MeSH)
• Mice (MeSH)
• Mice, Inbred C57BL (MeSH)
• Mice, Transgenic (MeSH)
• Motor Neurons (MeSH)
• Mutagenesis, Site-Directed (MeSH)
• Neurology & Neurosurgery (Science Metrix)
• Neuroprotective Agents (MeSH)
• Oncogene Protein v-akt (MeSH)
• RNA, Small Interfering (MeSH)
• Ribonuclease, Pancreatic (MeSH)
• Spinal Cord (MeSH)
• Superoxide Dismutase (MeSH)
• Time Factors (MeSH)
• Transfection (MeSH)
• Tunicamycin (MeSH)
• Wortmannin (MeSH)
• alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid (MeSH)

published in

• Journal of Neuroscience  Journal

keywords

• Amyotrophic Lateral Sclerosis
• Androstadienes
• Animals
• Cell Survival
• Cells, Cultured
• Disease Models, Animal
• Embryo, Mammalian
• Enzyme Inhibitors
• Excitatory Amino Acid Agonists
• Female
• Gene Expression
• Gene Expression Regulation
• Insulin-Like Growth Factor I
• Intercellular Adhesion Molecule-1
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Transgenic
• Motor Neurons
• Mutagenesis, Site-Directed
• Neuroprotective Agents
• Oncogene Protein v-akt
• RNA, Small Interfering
• Ribonuclease, Pancreatic
• Spinal Cord
• Superoxide Dismutase
• Time Factors
• Transfection
• Tunicamycin
• Wortmannin
• alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid

Digital Object Identifier (DOI)

• 10.1523/jneurosci.3399-08.2008

start page

• 14056

end page

• 14061

volume

• 28

issue

• 52