Docosahexaenoic acid (DHA) in stroke, Alzheimer’s disease, and blinding retinal degenerations: coping with neuroinflammation and sustaining cell survival

Abstract

The significance of the selective enrichment in omega-3 essential fatty acids in the nervous system has remained, until recently, incompletely understood. While studying mechanisms of cell survival in neurodegenerations, a new docosanoid synthesized from docosahexaenoic acid [DHA] by 15-lipoxygenase-1 [15-LOX-1] was discovered. This mediator, called neuroprotectin D1 [NPD1], is a docosanoid because it is derived from a 22C precursor (DHA), unlike eicosanoids, which are derived from the 20 C arachidonic acid family member of essential fatty acids not enriched in the nervous system. NPD1 is promptly made in response to oxidative stress and brain ischemiareperfusion and in the presence of neurotrophins. NPD1 is neuroprotective in experimental brain damage, oxidative-stressed retinal pigment epithelial [RPE] cells, and in human brain cells exposed to amyloid-b peptide. Thus NPD1 is a protective sentinel, one of the very first defenses activated when cell homeostasis is threatened by neurodegenerations. This review highlights the specificity and potency of NPD1 spanning beneficial bioactivity in experimental models of stroke, in retinal cells relevant to early events in age-related macular degenerations, and studies addressing fundamental issues during initiation and early progression of neurodegenerations.

Keywords

• ischemia-reperfusion
• neuroprotectin D1
• docosanoids
• retinal pigment epithelial cells
• photoreceptors