Cytochrome P450 Metabolism of Polyunsaturated Fatty Acids and Neurodegeneration

• Published in: Nutrients 2020-11, Vol.12 (11), p.3523
• Main Authors: Sarparast, Morteza, Dattmore, Devon, Alan, Jamie, Lee, Kin Sing Stephen
• Format: Article
• Language: English
• Subjects: Age; Aged; Aging; Aging - metabolism; Alzheimer's disease; Animals; Biosynthesis; Cytochrome; Cytochrome P-450 Enzyme System - metabolism; Cytochrome P450; Cytochromes P450; Diet; dietary intervention; Disease Models, Animal; Enzymes; epoxy-polyunsaturated fatty acid; Fatty acids; Fatty Acids, Omega-3 - administration & dosage; Fatty Acids, Omega-3 - metabolism; Fatty Acids, Omega-6 - administration & dosage; Fatty Acids, Omega-6 - metabolism; Health services; Humans; Medical treatment; Metabolism; Metabolites; Nervous system; Neurodegeneration; neurodegenerative disease; Neurodegenerative Diseases - metabolism; Neurodegenerative Diseases - prevention & control; Oxidative stress; Parkinson's disease; Physiology; polyunsaturated fatty acid; Polyunsaturated fatty acids; Proteins; Public health; Quality of Life; Review; Therapeutic targets
• ISSN: 2072-6643; 2072-6643
• DOI: 10.3390/nu12113523

Due to the aging population in the world, neurodegenerative diseases have become a serious public health issue that greatly impacts patients' quality of life and adds a huge economic burden. Even after decades of research, there is no effective curative treatment for neurodegenerative diseases. Polyunsaturated fatty acids (PUFAs) have become an emerging dietary medical intervention for health maintenance and treatment of diseases, including neurodegenerative diseases. Recent research demonstrated that the oxidized metabolites, particularly the cytochrome P450 (CYP) metabolites, of PUFAs are beneficial to several neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease; however, their mechanism(s) remains unclear. The endogenous levels of CYP metabolites are greatly affected by our diet, endogenous synthesis, and the downstream metabolism. While the activity of omega-3 (ω-3) CYP PUFA metabolites and omega-6 (ω-6) CYP PUFA metabolites largely overlap, the ω-3 CYP PUFA metabolites are more active in general. In this review, we will briefly summarize recent findings regarding the biosynthesis and metabolism of CYP PUFA metabolites. We will also discuss the potential mechanism(s) of CYP PUFA metabolites in neurodegeneration, which will ultimately improve our understanding of how PUFAs affect neurodegeneration and may identify potential drug targets for neurodegenerative diseases.