Abstract

Docosahexaenoic acid (DHA), an omega-3 essential fatty acid family member that is enriched in the nervous system, generates bioactive docosanoids that can counteract disruptions of cellular homeostasis. Docosanoids include neuroprotectin D1 (NPD1), which is decreased in the CA1 hippocampal area of patients with early-stage Alzheimers disease (AD). We summarize here how NPD1 elicits neuroprotection by up-regulating c-REL, a nuclear factor (NF)-kappaB subtype that, in turn, enhances expression of BIRC3 (baculoviral IAP repeat-containing protein 3, or cIAP2) in retinal cells. This DHA/NPD1-inducible pathway also is activated in an experimental ischemic stroke model and leads to neurological protection. Further elucidating the mechanisms of action of NPD1 and other docosanoids will contribute to managing diseases, including stroke, AD, age-related macular degeneration, traumatic brain injury, Parkinsons disease, and other neurodegenerative diseases.