PT  - JOURNAL ARTICLE
AU  - Kieran, Dairín
AU  - Sebastia, Jordi
AU  - Greenway, Matthew J.
AU  - King, Matthew A.
AU  - Connaughton, Dervla
AU  - Concannon, Caoimhin G.
AU  - Fenner, Beau
AU  - Hardiman, Orla
AU  - Prehn, Jochen H. M.
TI  - Control of Motoneuron Survival by Angiogenin
AID  - 10.1523/JNEUROSCI.3399-08.2008
DP  - 2008 Dec 24
TA  - The Journal of Neuroscience
PG  - 14056--14061
VI  - 28
IP  - 52
4099  - http://www.jneurosci.org/content/28/52/14056.short
4100  - http://www.jneurosci.org/content/28/52/14056.full
SO  - J. Neurosci.2008 Dec 24; 28
AB  - Mutations in the hypoxia-inducible factor angiogenin (ANG) have been identified in Amyotrophic Lateral Sclerosis (ALS) patients, but the potential role of ANG in ALS pathogenesis was undetermined. Here we show that angiogenin promotes motoneuron survival both in vitro and in 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-type ANG protected against endoplasmic reticulum (ER) stress-induced and trophic-factor-withdrawal-induced cell death in vitro, whereas the ALS-associated ANG mutant K40I exerted no protective activity and failed to activate Akt-1. In SOD1G93A mice 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.