The omega class glutathione S-transferases (GSTOs) are multifunctional enzymes involved in cellular defense and have distinct structural and functional characteristics, which differ from those of other GSTs. Previous studies provided evidence for the neuroprotective effects of GSTOs. However, the molecular mechanisms underpinning the neuroprotective functions of GSTOs have not been fully elucidated. Recently, our genetic and molecular studies using the Drosophila system have suggested that GstO1 has a protective function against H2O2-induced neurotoxicity by regulating the MAPK signaling pathway, and GstO2 is required for the activation of mitochondrial ATP synthase in the Drosophila neurodegenerative disease model. The comprehensive understanding of various neuroprotection mechanisms of Drosophila GstOs from our studies provides valuable insight into the neuroprotective functions of GstOs in vivo. In this review, we briefly introduce recent studies and summarize the novel biological functions and mechanisms underpinning neuroprotective effects of GstOs in Drosophila.
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