Year 3

5,910 small molecule compounds sourced from 4 libraries of small molecules with drug-like properties as well as 2 small molecule libraries with neuroprotective properties from unrelated screens were subject to screens to prevent formation of stress granules in neuronal cells. Stress granules are relevant to amyotrophic lateral sclerosis as mutations in RNA binding proteins lead to cytoplasmic aggregates precipitated by these stress granules. In this reporting period (since 6 months ago), ~10 compounds remain effective at inhibiting stress granule formation in counter screens and secondary assays. Successfully, we have shown that a subset of these compounds can reduce stress granules in mutant-containing IPSC-derived motor neuron models of ALS.