Journal Article


Jochen H M Prehn
Andreas Strasser
Andreas Villunger
Ina Woods
Dairin Kieran



animals apoptosis genetics mice metabolism puma protein mouse disease progression amyotrophic lateral sclerosis cell survival pathology physiology endoplasmic reticulum tumor suppressor proteins apoptosis regulatory proteins superoxide dismutase mice transgenic motor neurons gene deletion superoxide dismutase 1

Deletion of the BH3-only protein puma protects motoneurons from ER stress-induced apoptosis and delays motoneuron loss in ALS mice. (2007)

Abstract BH3-only proteins couple diverse stress signals to the evolutionarily conserved mitochondrial apoptosis pathway. Previously, we reported that the activation of the BH3-only protein p53-up-regulated mediator of apoptosis (Puma) was necessary and sufficient for endoplasmic reticulum (ER) stress- and proteasome inhibition-induced apoptosis in neuroblastoma and other cancer cells. Defects in protein quality control have also been suggested to be a key event in ALS, a fatal neurodegenerative condition characterized by motoneuron degeneration. Using the SOD1(G93A) mouse model as well as human post mortem samples from ALS patients, we show evidence for increased ER stress and defects in protein degradation in motoneurons during disease progression. Before symptom onset, we detected a significant up-regulation of Puma in motoneurons of SOD1(G93A) mice. Genetic deletion of puma significantly improved motoneuron survival and delayed disease onset and motor dysfunction in SOD1(G93A) mice. However, it had no significant effect on lifespan, suggesting that other ER stress-related cell-death proteins or other factors, such as excitotoxicity, necrosis, or inflammatory injury, may contribute at later disease stages. Indeed, further experiments using cultured motoneurons revealed that genetic deletion of puma protected motoneurons against ER stress-induced apoptosis but showed no effect against excitotoxic injury. These findings demonstrate that a single BH3-only protein, the ER stress-associated protein Puma, plays an important role during the early stages of chronic neurodegeneration in vivo.
Collections Ireland -> Royal College of Surgeons in Ireland -> PubMed

Full list of authors on original publication

Jochen H M Prehn, Andreas Strasser, Andreas Villunger, Ina Woods, Dairin Kieran

Experts in our system

Jochen H M Prehn
Royal College of Surgeons in Ireland
Total Publications: 206
Andreas Strasser
Royal College of Surgeons in Ireland
Total Publications: 7
Ina Woods
Royal College of Surgeons in Ireland
Total Publications: 16