Ile35 residue of SOD1 plays a key role in aggregate formation and eye degeneration in a Drosophila model of ALS
Year: 2026
Type: preprint
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 .
Language: English
Subfield: Clinical Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: green
Awards: Elucidation of regulation mechanisms of LLPS leading to pathological protein aggregation in neurodegenerative diseases, Elucidation of the molecular mechanism of ALS causative protein aggregate formation and pathogenesis, Elucidation of intracellular aggregation mechanism of ALS-causing protein and development of aggregation inhibitor, Elucidation of pathomechanisms and development of preventive therapies targeting protein LLPS for neurodegenerative diseases
OpenAlex ID: W7213762250