Elsevier

Molecular Aspects of Medicine

Volume 64, December 2018, Pages 18-33
Molecular Aspects of Medicine

Docosanoids and elovanoids from omega-3 fatty acids are pro-homeostatic modulators of inflammatory responses, cell damage and neuroprotection

https://doi.org/10.1016/j.mam.2018.09.003Get rights and content
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Abstract

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, pro-homeostatic cellular modulation, inflammatory responses, and innate immunity, opening avenues for prevention and therapeutic applications in neurotrauma, stroke and neurodegenerative diseases.

Keywords

Ischemic stroke
Retina degenerations
ELOVL4
Epileptogenesis
Alzheimer's disease
Parkinson's disease

Cited by (0)

Founder/Director, LSU Neuroscience Center of Excellence; Professor of Neurology; Yvette C./Ernest C. Villere Chair for Retinal Degenerations and Boyd Professor; Founder/Editor-in-Chief, Molecular Neurobiology; member of Founding Senate, DZNE (2009–2016, Germany); Board of Governors' Chairman Emeritus; ARVO Foundation; Foreign Adjunct Professor, Karolinska Institutet, Stockholm.

Awards include: Javits Neuroscience Investigator NINDS, NIH; Citation Classic, “Neural Stimulation or Onset of Cerebral Ischemia Activates Phospholipase A2” Current Contents, 1991; Elected, Royal Academy of Sciences, and of Medicine, Spain; Fellow, Royal College of Physicians,Ireland; Doctor Honoris Causa, Universidad Tucuman, Argentina; Endre Balazs Prize, ISER; Proctor Medal, ARVO; Chevreul Medal, France; Alkmeon International Prize; Miroslaw M. Mossakowski Medal, Polish Academy of Sciences.