Plasmalogens as biomarkers and therapeutic targets

Plasmalogens are structurally similar to phosphatidylcholine or phosphatidylethanolamine but differ at the Sn-1 position, containing a vinyl-ether instead of an ester bond. Reduced levels of plasmalogens in circulation or in cell membranes are associated with rare peroxisomal disorders, systemic disease, neurological impairment, cancer, and diseases of the heart, kidney, and liver. Roles for plasmalogens have been identified in lipid rafts, myelin, chlorolipids, bromolipids, hemostasis, cholesterol metabolism, and redox responses. The possible interconversion of plasmalogens into platelet-activating factor and the dysregulated activity of enzymes involved in the synthesis and catabolism of plasmalogens results in the reduced levels of these lipids during disease development. These enzymes also play dual roles in cell signaling, cellular respiratory homeostasis, innate immunity, inflammation, thrombosis, ferroptosis, autophagy, and neuron action potential. To further our understanding of plasmalogens as a biomarker and potential therapeutic, we have summarized clinical data on the role of these lipids in various diseases and the use of plasmalogens and their precursors in clinical trials. We also describe the complexities of plasmalogen synthesis and catabolism and detail aspects of these pathways in specific diseases that identify plasmalogens as a biomarker. Lastly, we summarize current and future research to better harness the effects of plasmalogens in the pathogenesis and treatment of systemic and/or organ-specific disease.