Qualified MBBS: 2013
The role of AP-1 transcription factor c-jun in Amyotrophic Lateral Sclerosis (ALS)
Prof Gennadij Raivich, Institute for Women's Health
Motor Neurone Disease Ass Prize
Description of Project:
Mutations in the ubiquitously expressed SOD1 gene are a cause familial ALS. Transgenic mice carrying SOD1G93A mutations develop an adult onset form of lethal motor neuron disease. The proto-oncoprotein c-Jun is involved in neuronal survival and regeneration and its presence at increased levels in the spinal motoneurons of ALS patients and mouse models suggests it may play a role in this neurodegenerative disease. To study the role of c-jun in ALS, we crossed conditional mouse mutants lacking c-jun in the CNS with transgenic SOD1G93A mice. Our preliminary data demonstrates that the deletion of c-jun results in a significant increase in lifespan and reduction in ALS pathology in SODG93A mice. Further investigations will concentrate on the cellular and molecular mechanisms through which c-jun deletion is neuroprotective and in the possible pharmacological interventions against c-jun that may ameliorate ALS pathology.
. ACOSTA-SALTOS, M. MAKWANA, A. GILCHRIST, C. DA COSTA, A. BEHRENS, G. RAIVICH. Neuronal deletion of c-jun in amyotrophic lateral sclerosis (ALS) Cu/Zn superoxide dismutase 1 SODG93A transgenic mice reduces neuronal cell death, gliosis and prolongs lifespan. Program No.136.18.