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

• DOI: 10.1101/2023.10.02.560527
• Publication Date: 2023-10-03T02:40:11Z
• Authors: Morteza Sarparast; Jennifer Hinman; Elham Pourmand; Derek Vonarx; Leslie Ramirez; Wenjuan Ma; Nicole F. Liachko; Jamie K. Alan; Kin Sing Stephen Lee

ABSTRACTThis 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 utilizingCaenorhabditis elegans(C. elegans) as a model organism. Our research reveals that Aβ and/or tau expression inC. elegansdisrupts 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 inC. elegansphysiology, opening up possibilities for broader implications in mammalian and human contexts.Abstract Figure