Cytochrome P450 and Epoxide Hydrolase Metabolites in Aβ and tau-induced Neurodegeneration: Insights from Caenorhabditis elegans

This study aims to uncover potent cytochrome P450 (CYP) and epoxide hydrolase (EH) metabolites implicated in Aβ and/or tau-induced neurodegeneration, independent of neuroinflammation, by utilizing Caenorhabditis elegans (C. elegans) as a model organism. Our research reveals that Aβ and/or tau expression in C. elegans disrupts the oxylipin profile, and epoxide hydrolase inhibition alleviates the ensuing neurodegeneration, likely through elevating the epoxy-to-hydroxy ratio of various CYP-EH metabolites. These findings emphasize the intriguing relationship between lipid metabolites and neurodegenerations, in particular those are linked to Aβ and/or tau aggregation. Furthermore, our investigation sheds light on the crucial and captivating role of CYP PUFA metabolites in C. elegans physiology, opening up possibilities for broader implications in mammalian and human contexts. ### Competing Interest Statement The authors have declared no competing interest.