protectin-d1 and Nerve-Degeneration

Stroke severely impairs quality of life and has a high mortality rate. On the other hand, dietary docosahexaenoic acid (DHA) prevents neuronal damage. In this review, we describe the effects of dietary DHA on ischemic stroke-associated neuronal damage and its role in stroke prevention. Recent epidemiological studies have been conducted to analyze stroke prevention through DHA intake. The effects of dietary intake and supply of DHA to neuronal cells, DHA-mediated inhibition of neuronal damage, and its mechanism, including the effects of the DHA metabolite, neuroprotectin D1 (NPD1), were investigated. These studies revealed that DHA intake was associated with a reduced risk of stroke. Moreover, studies have shown that DHA intake may reduce stroke mortality rates. DHA, which is abundant in fish oil, passes through the blood-brain barrier to accumulate as a constituent of phospholipids in the cell membranes of neuronal cells and astrocytes. Astrocytes supply DHA to neuronal cells, and neuronal DHA, in turn, activates Akt and Raf-1 to prevent neuronal death or damage. Therefore, DHA indirectly prevents neuronal damage. Furthermore, NDP1 blocks neuronal apoptosis. DHA, together with NPD1, may block neuronal damage and prevent stroke. The inhibitory effect on neuronal damage is achieved through the antioxidant (via inducing the Nrf2/HO-1 system) and anti-inflammatory effects (via promoting JNK/AP-1 signaling) of DHA.

Topics: alpha-Linolenic Acid; Animals; Anti-Inflammatory Agents; Antioxidants; Apoptosis; Biological Availability; Biological Transport; Blood-Brain Barrier; Brain Damage, Chronic; Dietary Fats; Docosahexaenoic Acids; Fatty Acid-Binding Proteins; Fish Oils; Humans; Incidence; Ischemic Stroke; Membrane Lipids; Mice; Neoplasm Proteins; Nerve Degeneration; Nerve Tissue Proteins; Neurons; Plant Oils; Signal Transduction; Stroke; Symporters

Recent data have provided important clues about the molecular mechanisms underlying certain retinal degenerative diseases, including retinitis pigmentosa and age-related macular degeneration. Photoreceptor cell degeneration is a feature common to these diseases, and the death of these cells in many instances seems to involve the closely associated retinal pigment epithelial (RPE) cells. Under normal circumstances, both cell types are subject to potentially damaging stimuli (e.g. sunlight and high oxygen tension). However, the mechanism or mechanisms by which homeostasis is maintained in this part of the eye, which is crucial for sight, are an unsolved riddle. The omega-3 fatty acid family member docosahexaenoic acid (DHA), which is enriched in these cells, is the precursor of neuroprotectin D1 (NPD1). NPD1 inhibits oxidative-stress-mediated proinflammatory gene induction and apoptosis, and consequently promotes RPE cell survival. This enhanced understanding of the molecular basis of endogenous anti-inflammatory and neuroprotective signaling in the RPE presents an opportunity for the development of therapies for retinal degenerative diseases.

Topics: Animals; Cell Death; Cell Survival; Docosahexaenoic Acids; Humans; Nerve Degeneration; Oxidative Stress; Photoreceptor Cells; Pigment Epithelium of Eye; Retinal Degeneration; Signal Transduction