Polyunsaturated Fatty Acid Deuteration against Neurodegeneration

Abstract

Oxidative stress is a common feature of genetic and idiopathic neurological diseases that thus far have been intractable to drug therapy. Polyunsaturated fatty acids (PUFAs) form cellular, mitochondrial, retinal, and other membranes highly important in neuronal function. However, PUFAs are susceptible to the noxious lipid peroxidation (LPO) chain reaction, which is a common feature of various neurological and age-related pathologies, making this pathway an attractive target for therapeutic intervention. Regioselective deuteration that reinforces oxidation-prone, bis-allylic sites of PUFAs is a novel, nonantioxidant treatment modality that dramatically reduces LPO, potentially mitigating numerous diseases through preservation of membrane properties and amelioration of oxidative stress. Animal disease models and several ongoing human clinical trials highlight the potential of the deuterated-PUFA (D-PUFA) drug candidates currently in development.

Keywords: deuterium; lipid membrane; lipid peroxidation; neurological disease; polyunsaturated fatty acid; reactive oxygen species.