Alkylglycerol Lipid Precursors: A Review of Therapeutic Strategies for Plasmalogen Replacement

Plasmalogens are unique vinyl ether glycerophospholipids that serve diverse structural roles in the membranes of cells and cell organelles. Additionally, the fatty acid substitutions at sn– 2 of the glycerol backbone are dynamically removed by lipases and replaced by acyltransferases. These fatty acid storage pools provide the free arachidonic acid and docosahexaenoic acid (DHA) involved in signal transduction cascades. The biosynthesis of plasmalogens critically involves the generation of the ether lipid substitution at sn-1 of the glycerol backbone. This step only occurs in peroxisomes and is dysfunctional in genetic peroxisomal disorders and in several diseases of aging. A number of approaches have been undertaken to augment plasmalogen levels in these clinical conditions. In this review we present the current status of alkylglycerol precursors that bypass the requirement of the peroxisomal compartment.