RT Journal Article
SR Electronic
T1 Control of Motoneuron Survival by Angiogenin
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 14056
OP 14061
DO 10.1523/JNEUROSCI.3399-08.2008
VO 28
IS 52
A1 Kieran, Dairín
A1 Sebastia, Jordi
A1 Greenway, Matthew J.
A1 King, Matthew A.
A1 Connaughton, Dervla
A1 Concannon, Caoimhin G.
A1 Fenner, Beau
A1 Hardiman, Orla
A1 Prehn, Jochen H. M.
YR 2008
UL http://www.jneurosci.org/content/28/52/14056.abstract
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.