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Abstract
<p class="first" id="P1">The functional significance of the selective enrichment of
the omega-3 essential fatty
acid docosahexaenoic acid (DHA; 22C and 6 double bonds) in cellular membrane phospholipids
of the nervous system is being clarified by defining its specific roles on membrane
protein function and by the uncovering of the bioactive mediators, docosanoids and
elovanoids (ELVs). Here, we describe the preferential uptake and DHA metabolism in
photoreceptors and brain as well as the significance of the Adiponectin receptor 1
in DHA retention and photoreceptor cell (PRC) survival. We now know that this integral
membrane protein is engaged in DHA retention as a necessary event for the function
of PRCs and retinal pigment epithelial (RPE) cells. We present an overview of how
a) NPD1 selectively mediates preconditioning rescue of RPE and PR cells; b) NPD1 restores
aberrant neuronal networks in experimental epileptogenesis; c) the decreased ability
to biosynthesize NPD1 in memory hippocampal areas of early stages of Alzheimer’s disease
takes place; d) NPD1 protection of dopaminergic circuits in an in vitro model using
neurotoxins; and e) bioactivity elicited by DHA and NPD1 activate a neuroprotective
gene-expression program that includes the expression of Bcl-2 family members affected
by Aβ42, DHA, or NPD1. In addition, we highlight ELOVL4 (ELOngation of Very Long chain
fatty acids-4), specifically the neurological and ophthalmological consequences of
its mutations, and their role in providing precursors for the biosynthesis of ELVs.
Then we outline evidence of ELVs ability to protect RPE cells, which sustain PRC integrity.
In the last section, we present a summary of the protective bioactivity of docosanoids
and ELVs in experimental ischemic stroke. The identification of early mechanisms of
neural cell survival mediated by DHA-synthesized ELVs and docosanoids contributes
to the understanding of cell function, prohomeostatic cellular modulation, inflammatory
responses, and innate immunity, opening avenues for prevention and therapeutic applications
in neurotrauma, stroke and neurodegenerative diseases.
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