4.8 Article

Elovanoids are a novel class of homeostatic lipid mediators that protect neural cell integrity upon injury

Journal

SCIENCE ADVANCES
Volume 3, Issue 9, Pages -

Publisher

AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/sciadv.1700735

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Funding

  1. National Institute of Neurological Disorders and Stroke [NS046741]
  2. National Institute of General Medical Sciences [GM103340]
  3. Arthur C. Cope Scholar Fund

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We report the characterization of a novel class of lipid mediators termed elovanoids (ELVs) (ELV-N32 and ELV-N34), which are dihydroxylated derivatives of 32:6n3 and 34:6n3, respectively. The precursors of ELVs are made by elongation of a 22:6n3 fatty acid and catalyzed by ELOVL4 (elongation of very-long-chain fatty acids-4). The structure and stereochemistry of ELVs were established using synthetic compounds produced by stereocontrolled total synthesis. We report that ELV-mediated protection is induced in neuronal cultures undergoing either oxygen/glucose deprivation or N-methyl-D-aspartate receptor-mediated excitotoxicity, as well as in experimental ischemic stroke. The methyl ester or sodium salt of ELV-N32 and ELV-N34 resulted in reduced infarct volumes, promoted cell survival, and diminished neurovascular unit disruption when administered 1 hour following 2 hours of ischemia by middle cerebral artery occlusion. Together, our data reveal a novel prohomeostatic and neuroprotective lipid-signaling mechanism aiming to sustain neural cell integrity.

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