Yanagi, Katherine et al. (2021) International Worm Meeting "Suppressors of stress-induced glutamatergic neuron degeneration in sod-1G85R ALS model"

Mahapatra, Animesh, Walsh, Melissa, Tsai, Jason, Hart, Anne, Lins, Jeremy, Yanagi, Katherine, Stinson, Loraina, Kruskop, Jane, Osborne, Jennifer

[International Worm Meeting, 2021]

Amyotrophic Lateral Sclerosis (ALS) is one of the most common adult-onset neurodegenerative disorders that results from the selective and progressive degeneration of cortical and spinal motor neurons. Mutations over 20 genes including RNA binding proteins, FUS and TDP43, and a free radical scavenger, superoxide dismutase 1 (SOD1) cause ALS. Although there is a well-established genetic component of ALS, it is still unclear why mutations in genes encoding functionally diverse proteins cause motor neuron degeneration. Identifying modifiers of neurodegeneration in C. elegans ALS models may provide insight into the mechanisms behind the selective and progressive neurodegeneration in ALS. Here, we have undertaken a classical forward genetic screen to identify suppressors of glutamatergic neuron degeneration. After exposure to oxidative stress, SOD-1G85R knock-in mutants have both glutamatergic and cholinergic neuron degeneration (PMC6200258). We mutagenized SOD-1G85R animals and screened for suppressors of glutamatergic neuron degeneration. After whole genome sequencing, we found that an RNA binding protein, hit in three independently isolated lines, suppresses cholinergic and glutamatergic neuron degeneration. Understanding the relationship between SOD1 and RNA binding proteins will provide insight if there are common mechanisms underlying neurodegeneration in ALS and has the potential to facilitate the development of treatments.