Understanding motoneuron cell death in ALS using the fruit fly Drosophila melanogaster
Motoneuronal cell death is a hallmark of amyotrophic lateral sclerosis (ALS). In ALS, all neurons have the same mutations, yet it is unclear why motoneurons preferentially die. Mutations in the superoxide dismutase 1 (SOD1) gene are implicated in ~12% of familial ALS cases. Loss of SOD1 leads to the build-up of free radicals and oxidative stress. We hypothesize that motoneurons die due to oxidative stress and a secondary stressor: action potential firing. Neuronal activity uses ATP, and ATP regeneration stimulates free radicals and oxidative stress. Using Drosophila, we found that increasing neuronal activity and using an RNAi knockdown of SOD1 reduces lifespan and increases cell death markers. We have created GFP-expressing animals to compare motoneuron cell death to a control population (mushroom body Kenyon cells). We are currently focusing on Kenyon cells of the adult fly and we expect this work to address cell type-dependent effects on cell death.
Keywords: Drosophila, cell death, SOD1, ALS
Topic(s):Biology
Presentation Type: Asynchronous Virtual Poster
Session: 4-13
Location: https://flipgrid.com/7ba08930
Time: 0:00