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

Abstract

This study aims to uncover potent cytochrome P450 (CYP) and epoxide hydrolase (EH) metabolites implicated in A{beta} and/or tau-induced neurodegeneration, independent of neuroinflammation, by utilizing Caenorhabditis elegans (C. elegans) as a model organism. Our research reveals that A{beta} 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. In addition, our results indicated that the A{beta} 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 A{beta} 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. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=92 SRC="FIGDIR/small/560527v1_ufig1.gif" ALT="Figure 1"> View larger version (22K): org.highwire.dtl.DTLVardef@8fd3fdorg.highwire.dtl.DTLVardef@a6c4e1org.highwire.dtl.DTLVardef@c7a5a7org.highwire.dtl.DTLVardef@14c8ce2_HPS_FORMAT_FIGEXP M_FIG C_FIG