Erucic acid, a nutritional PPARδ-ligand may influence Huntington's disease pathogenesis

Increasing recent evidence suggests a key role of oligodendroglial injury and demyelination in the pathophysiology of Huntington's Disease (HD) and the transcription factor PPARδ is critical for oligodendroglial regeneration and myelination. PPARδ directly involves in the pathogenesis of HD and treatment with a brain-permeable PPARδ-agonist (KD3010) alleviates its severity in mice. Erucic acid (EA) is also a PPARδ-ligand ω9 fatty acid which is highly consumed in Asian countries through ingesting cruciferous vegetables such as rapeseed (Brassica napus) and indian mustard (Brassica juncea). EA is also an ingredient of Lorenzo's oil employed in the medical treatment of adrenoleukodystrophy and can be converted to nervonic acid, a component of myelin. HD pathogenesis also involves oxidative and inflammatory injury and EA exerts antioxidative and antiinflammatory efficacies including inhibition of thrombin and elastase. Consumption of rapeseed, indian mustard, and Canola oils (containing EA) improves cognitive parameters in animal models, as well as treatment with pure EA. Moreover, erucamide, an endogenous EA-amide derivative regulating angiogenesis and water balance, exerts antidepressive and anxiolytic effects in mice. Hitherto, no study has investigated the therapeutic potential of EA in HD and we believe that it strongly merits to be studied in animal models of HD as a potential therapeutic.