PPAR-δ and erucic acid in multiple sclerosis and Alzheimer's Disease. Likely benefits in terms of immunity and metabolism

Int Immunopharmacol. 2019 Apr;69:245-256. doi: 10.1016/j.intimp.2019.01.057. Epub 2019 Feb 8.


The transcription factor, PPARδ is involved in suppressing inflammation, stimulating oligodendroglial biogenesis and myelination. Furthermore, activation of PPARδ directly protects mitochondria against noxious stimuli and stimulates biogenesis of new mitochondria. PPARδ activation directly inhibits neuronal cell death and reduces both the level and neurotoxicity of Amyloid-β fibers in Alzheimer's Disease (AD) models. Among the important ligands of PPARδ is erucic acid (EA, 22:1 n9), an edible omega-9 fatty acid and a component of Lorenzo's oil, which is used in the treatment of adrenoleukodystrophy (ALD). Nonetheless, the feature of PPARδ-erucic acid interaction has not been extensively studied. EA can also be converted to nervonic acid, an important component of myelin. Hence, EA may act as an anti-inflammatory and remyelinating agent, which might be important in the management of another demyelinating disease, multiple sclerosis (MS). Oxidative injury and mitochondrial damage are among the features of ALD. Direct inhibitory effects of EA was observed on lipid peroxidation and inflammatory enzymes, neutrophil elastase and thrombin. EA also induces catalase, a potent antioxidant peroxisomal enzyme. However, EA is claimed to be a cardiotoxic molecule, yet these studies were mostly performed on rats, which do not efficiently metabolize EA. Further, EA is largely consumed by Asian population and Greenland Eskimos with no signs of cardiac damage. In this review, we shed light on the potential theraputic role of EA in MS and AD by blocking neural cell death, mitigating neuroinflammation and/or inducing myelination.

Keywords: Alzheimer's Disease; Erucic acid; Multiple sclerosis; Neuroprotection; PPAR-delta; Remyelination.

Publication types

  • Review

MeSH terms

  • Adrenoleukodystrophy / immunology*
  • Alzheimer Disease / immunology*
  • Animals
  • Cardiotoxicity
  • Drug Combinations
  • Erucic Acids / metabolism*
  • Humans
  • Immunity
  • Ligands
  • Lipid Peroxidation
  • Mitochondria / metabolism*
  • Multiple Sclerosis / immunology*
  • Oxidative Stress
  • PPAR delta / metabolism*
  • Rats
  • Triolein


  • Drug Combinations
  • Erucic Acids
  • Ligands
  • Lorenzo's oil
  • PPAR delta
  • erucic acid
  • Triolein