Molecular mechanisms of signaling via the docosanoid neuroprotectin D1 for cellular homeostasis and neuroprotection

J Biol Chem. 2017 Jul 28;292(30):12390-12397. doi: 10.1074/jbc.R117.783076. Epub 2017 Jun 14.

Abstract

Docosahexaenoic acid, enriched in the brain and retina, generates docosanoids in response to disruptions of cellular homeostasis. Docosanoids include neuroprotectin D1 (NPD1), which is decreased in the CA1 hippocampal area of patients with early-stage Alzheimer's disease (AD). We summarize here how NPD1 elicits neuroprotection by up-regulating c-REL, a nuclear factor (NF)-κB subtype that, in turn, enhances expression of BIRC3 (baculoviral inhibitor of apoptosis repeat-containing protein 3) in the retina and in experimental stroke, leading to neuroprotection. Elucidating the mechanisms of action of docosanoids will contribute to managing diseases, including stroke, AD, age-related macular degeneration, traumatic brain injury, Parkinson's disease, and other neurodegenerations.

Keywords: NF-kB transcription factor; cell death; lipid signaling; neurodegenerative disease; retina.

Publication types

  • Review
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Docosahexaenoic Acids / metabolism*
  • Homeostasis*
  • Humans
  • Neuroprotection*
  • Proto-Oncogene Proteins c-rel / metabolism
  • Signal Transduction*

Substances

  • Proto-Oncogene Proteins c-rel
  • protectin D1
  • Docosahexaenoic Acids