triolein and Alzheimer-Disease

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.

Topics: Adrenoleukodystrophy; Alzheimer Disease; Animals; Cardiotoxicity; Drug Combinations; Erucic Acids; Humans; Immunity; Ligands; Lipid Peroxidation; Mitochondria; Multiple Sclerosis; Oxidative Stress; PPAR delta; Rats; Triolein

Alzheimer's disease (AD) brains are characterized by accumulation of amyloid beta protein (Abeta) and neuroinflammation. Increased blood-to-brain influx and decreased brain-to-blood efflux across the blood-brain barrier (BBB) have been proposed as mechanisms for Abeta accumulation. Epidemiological studies suggest that the nonsteroidal anti-inflammatory drug (NSAID) indomethacin slows the progression of AD. We hypothesized that inflammation alters BBB handling of Abeta. Mice treated with lipopolysaccharide (LPS) had increased brain influx and decreased brain efflux of Abeta, recapitulating the findings in AD. Neither influx nor efflux was mediated by LPS acting directly on BBB cells. Increased influx was mediated by a blood-borne factor, indomethacin-independent, blocked by the triglyceride triolein, and not related to expression of the blood-to-brain transporter of Abeta, RAGE. Serum levels of IL-6, IL-10, IL-13, and MCP-1 mirrored changes in Abeta influx. Decreased efflux was blocked by indomethacin and accompanied by decreased protein expression of the brain-to-blood transporter of Abeta, LRP-1. LPS paradoxically increased expression of neuronal LRP-1, a major source of Abeta. Thus, inflammation potentially increases brain levels of Abeta by three mechanisms: increased influx, decreased efflux, and increased neuronal production.

Topics: Alzheimer Disease; Amyloid beta-Peptides; Animals; Blood-Brain Barrier; Blotting, Western; Brain; Cyclooxygenase Inhibitors; Cytokines; Disease Progression; Dose-Response Relationship, Drug; Indomethacin; Inflammation; Lipopolysaccharides; Low Density Lipoprotein Receptor-Related Protein-1; Male; Mice; Oxidative Stress; Protein Transport; Receptor for Advanced Glycation End Products; Receptors, Immunologic; Receptors, LDL; Triolein; Tumor Suppressor Proteins