| Autor: |
Sarparast M; Department of Pharmacology and Toxicology, Michigan State University, East Lansing, MI, USA.; Department of Chemistry, Michigan State University, East Lansing, MI, USA., Hinman J; Department of Chemistry, Michigan State University, East Lansing, MI, USA.; Institute of Integrative Toxicology, Michigan State University, East Lansing, MI, USA., Pourmand E; Department of Chemistry, Michigan State University, East Lansing, MI, USA., Vonarx D; Department of Chemistry, Michigan State University, East Lansing, MI, USA., Ramirez L; Department of Pharmacology and Toxicology, Michigan State University, East Lansing, MI, USA., Ma W; Center for Statistical Training and Consulting (CSTAT), Michigan State University, East Lansing, MI, USA., Liachko NF; Geriatrics Research Education and Clinical Center, Veterrans Affairs Puget Sound Health Care System, Seattle, WA, USA.; Division of Gerontology and Geriatric Medicine, Department of Medicine, University of Washington, Seattle, WA, USA., Alan JK; Department of Pharmacology and Toxicology, Michigan State University, East Lansing, MI, USA., Lee KSS; Department of Pharmacology and Toxicology, Michigan State University, East Lansing, MI, USA.; Department of Chemistry, Michigan State University, East Lansing, MI, USA.; Institute of Integrative Toxicology, Michigan State University, East Lansing, MI, USA. |
| Abstrakt: |
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. 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 C. elegans physiology, opening up possibilities for broader implications in mammalian and human contexts. |
