Abstract
Omega-3 polyunsaturated fatty acids (PUFAs) exhibit neuroprotective properties and represent a potential treatment for a variety of neurodegenerative and neurological disorders. However, traditionally there has been a lack of discrimination between the different omega-3 PUFAs and effects have been broadly accredited to the series as a whole. Evidence for unique effects of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and more recently docosapentaenoic acid (DPA) is growing. For example, beneficial effects in mood disorders have more consistently been reported in clinical trials using EPA; whereas, with neurodegenerative conditions such as Alzheimer’s disease, the focus has been on DHA. DHA is quantitatively the most important omega-3 PUFA in the brain, and consequently the most studied, whereas the availability of high purity DPA preparations has been extremely limited until recently, limiting research into its effects. However, there is now a growing body of evidence indicating both independent and shared effects of EPA, DPA and DHA. The purpose of this review is to highlight how a detailed understanding of these effects is essential to improving understanding of their therapeutic potential. The review begins with an overview of omega-3 PUFA biochemistry and metabolism, with particular focus on the central nervous system (CNS), where DHA has unique and indispensable roles in neuronal membranes with levels preserved by multiple mechanisms. This is followed by a review of the different enzyme-derived anti-inflammatory mediators produced from EPA, DPA and DHA. Lastly, the relative protective effects of EPA, DPA and DHA in normal brain aging and the most common neurodegenerative disorders are discussed. With a greater understanding of the individual roles of EPA, DPA and DHA in brain health and repair it is hoped that appropriate dietary recommendations can be established and therapeutic interventions can be more targeted and refined.
Highlights
There is mounting evidence supporting the beneficial effects of an increased intake of omega-3 polyunsaturated fatty acids (PUFAs) in a variety of neurodegenerative and neurological conditions (Dyall and Michael-Titus, 2008; Dyall, 2010; Denis et al, 2015)
The oxygenated docosahexaenoic acid (DHA)-derivative NPD1 has been shown to promote neuronal differentiation of embryonic stem cells (Yanes et al, 2010). These results suggest that the regulatory effects of eicosapentaenoic acid (EPA) and DHA directing neural stem cell fate are mediated via divergent effects at transcription factors and potentially different signaling pathways, and may be at least in part mediated by their enzymatic conversion to bioactive mediators
EPA, docosapentaenoic acid (DPA) and DHA differ in important aspects of their biochemistry and metabolism; few studies have made direct comparisons between their effects
Summary
There is mounting evidence supporting the beneficial effects of an increased intake of omega-3 polyunsaturated fatty acids (PUFAs) in a variety of neurodegenerative and neurological conditions (Dyall and Michael-Titus, 2008; Dyall, 2010; Denis et al, 2015). A number of excellent reviews have discussed the complementary and divergent effects of the different omega-3 PUFAs both at the fundamental level in terms of cell signaling and function (Gorjão et al, 2009; Russell and Bürgin-Maunder, 2012), and in diseases such as cancer, insulin resistance, and cardiovascular disease (Anderson and Ma, 2009; Mozaffarian and Wu, 2012). The aim of this current article is to review the effects of the different long-chain omega-3 PUFAs in the brain in normal aging and neurodegenerative disorders. In the peroxisome 24:6n-3 is shortened to DHA (22:6n-3) by a single round of β-oxidation by the action of acyl-coenzyme-A oxidase (ACOX1 gene), D-bifunctional enzyme (HSD1784 gene) and peroxisomal thiolases
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