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

• Published in: bioRxiv : the preprint server for biology
• Main Authors: Sarparast, Morteza, Hinman, Jennifer, Pourmand, Elham, Vonarx, Derek, Ramirez, Leslie, Ma, Wenjuan, Liachko, Nicole F, Alan, Jamie K, Lee, Kin Sing Stephen
• Format: Journal Article
• Language: English
• Published: United States 02.10.2023
• DOI: 10.1101/2023.10.02.560527

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 ( ) as a model organism. Our research reveals that Aβ and/or tau expression in 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. In addition, our results indicated that the Aβ and tau likely affect the CYP-EH metabolism of PUFA through different mechanism. These findings emphasize the intriguing relationship between lipid metabolites and neurodegenerations, in particular, those linked to Aβ and/or tau aggregation. Furthermore, our investigation sheds light on the crucial and captivating role of CYP PUFA metabolites in physiology, opening up possibilities for broader implications in mammalian and human contexts.