Neuroprotectin D1-mediated anti-inflammatory and survival signaling in stroke, retinal degenerations, and Alzheimer's disease

Abstract

Docosahexaenoic acid (DHA), the main omega-3 fatty acid, is concentrated and avidly retained in membrane phospholipids of the nervous system. DHA is involved in brain and retina function, aging, and neurological and psychiatric/ behavioral illnesses. Neuroprotectin D1 (NPD1), the firstidentified stereoselective bioactive product of DHA, exerts neuroprotection in models of experimental stroke by downregulating brain ischemia reperfusion (BIR)-induced leukocyte infiltration, proinflammatory signaling, and infarct size. Moreover, NPD1 inhibits cytokine-mediated cyclooxygenase-2

Docosahexaenoic acid is a beneficial replacement treatment for spinocerebellar ataxia 38

“…Our data are in agreement with the hypothesis that DHA intake, acting directly on ELOVL5 expression, reduces mutant ELOVL5 cellular levels, as indicated by a decrease of ELOVL5 expression in patients’ blood after 40‐week DHA treatment. Furthermore, a general neuroprotective effect of DHA may occur, by promoting brain cell survival and repair through neurotrophic, antiapoptotic, and anti‐inflammatory signaling 23. As expected, DHA administration was safe and no side effect was reported.…”

Docosahexaenoic Acid (DHA), in the Prevention and Treatment of Neurodegenerative Diseases

“…However, as ageing progress and during the development of neurodegenerative diseases, a significant reduction in the DHA content of the brain is produced (Tully et al, 2003), especially in the cortex, cerebellum and hypothalamus, which result in a considerable reduction in the fluidity of neuronal membranes and an alteration of the neuronal homeostasis (Sodeberg et al, 1991;Kalminj et al, 2004). Beyond the effect of DHA at the neuronal membranes, the fatty acid also exerts other protective effects which are mediated by a metabolic derivative named neuroprotectin D-1 (NPD-1) which may protect neurons against oxidative stress, inflammation, disruption of the cytoskeleton and from the activation of apoptotic signaling pathways (Bazan, 2009). NPD-1, formed from DHA, is normally present in the nervous system, especially in the brain, but it is especially relevant 128 in states and/or situations that may compromise the activity, integrity and neuronal viability, as it is the case of neurodegenerative diseases, brain injury by ischemiareperfusion, leukocyte infiltration and activation of proapoptotic signaling pathways (Bazan, 2009;Belayev et al, 2009).…”

“…Beyond the effect of DHA at the neuronal membranes, the fatty acid also exerts other protective effects which are mediated by a metabolic derivative named neuroprotectin D-1 (NPD-1) which may protect neurons against oxidative stress, inflammation, disruption of the cytoskeleton and from the activation of apoptotic signaling pathways (Bazan, 2009). NPD-1, formed from DHA, is normally present in the nervous system, especially in the brain, but it is especially relevant 128 in states and/or situations that may compromise the activity, integrity and neuronal viability, as it is the case of neurodegenerative diseases, brain injury by ischemiareperfusion, leukocyte infiltration and activation of proapoptotic signaling pathways (Bazan, 2009;Belayev et al, 2009). In this context, NPD-1 has anti-inflammatory, antiapoptotic and even neuroregenerative effects, which would help to preserve in general, both the neuronal functioning and the nervous system (Reinoso et al 2008).…”

“…The greatest evidence about the neuroprotective effect of DHA has been observed in Alzheimer's disease. DHA may suppress the cytotoxic effects of the accumulation of the β-amyloid peptide, being the main mechanism associated to the neuroprotective action of the fatty acid (Bazan, 2009;Reinoso et al, 2008). Facing this evidence, it is reasonable to consider the beneficial effect of increasing the consumption of DHA by eating foods rich in the fatty acid, such as fatty fish or DHA containing supplements.…”

Lipid Mediators in Life Science

“…Pioneered by Serhan and Bazan, these ω-3 lipid mediators such as resolvins, protectins and maresins, as well as lipoxins derived from ω-6 aa, have recently attracted considerable attention as critical mediators of the resolution of inflammation [6,68]. Biosynthesis of these anti-inflammatory lipid mediators from PuFas involves 12/15-LOX and other enzymes acting upstream and downstream of 12/15-LOX that have not yet been fully identified.…”