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Knockdown of glutathione S-transferase leads to mislocalization and accumulation of cabeza, a drosophila homolog of FUS, in the brain

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Therapeutic modulation of GSTO activity rescues FUS-associated neurotoxicity via deglutathionylation in ALS disease models

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Summary: Using a Drosophila model, researchers found that overexpression of glutathione transferase omega 2 (GstO2) reduces aggregation of Fused in sarcoma (FUS) protein and prevents associated neurodegenerative phenotypes. They identified a glutathionylation site on FUS that promotes aggregation through phase separation. In mouse neuronal cells, overexpression of human GSTO1, a homolog of GstO2, also reduces FUS-induced neurotoxicity and cytoplasmic aggregation. These findings suggest that modulation of FUS glutathionylation could be a promising therapeutic strategy for FUS-associated neurodegenerative diseases.

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