Ile35 residue of SOD1 plays a key role in aggregate formation and eye degeneration in a <i>Drosophila</i> model of ALS

Abstract The pathophysiology of ALS caused by mutant SOD1 remains unclear. We previously demonstrated, using the BioID2-EGFP sandwich expression system in cultured cells, that the Ile35 residue of ALS-linked mutant SOD1 promotes its aggregate formation. However, the precise role of the SOD1 Ile35 residue in aggregate formation and neurodegeneration in vivo remained unclear. Drosophila expressing BioID2-G93A-EGFP demonstrated aggregate formation and eye degeneration with reduced eye size, whereas those expressing BioID2-G93A/I35S-EGFP showed less of these phenotypes. These findings highlight the crucial role of the Ile35 residue of ALS-linked SOD1 in aggregate formation and neurodegeneration in vivo .