DHA/EPA (Omega-3) and LA/GLA (Omega-6) as Bioactive Molecules in Neurodegenerative Diseases

Abstract

Neurodegenerative diseases are characterized by neuroinflammation, neuronal depletion and oxidative stress. They coincide with subtle chronic or flaring inflammation, sometimes escalating with infiltrations of the immune system cells in the inflamed parts causing mild to severe or even lethal damage. Thus, neurodegenerative diseases show all features of autoimmune diseases. Prevalence of neurodegenerative diseases has dramatically increased in recent decades and unfortunately, the therapeutic efficacy and safety profile of available drugs is moderate. The beneficial effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) polyunsaturated fatty acids (omega-3 PUFAs) are nowadays highlighted by a plethora of studies. They play a role in suppression of inflammation, gene expression, cellular membrane fluidity/permeability, immune functionality and intracellular/exocellular signaling. The role of omega-6 polyunsaturated fatty acids, such as linoleic acid (LA), gamma linolenic acid (GLA), and arachidonic acid (AA), on neuroprotection is controversial, as some of these agents, specifically AA, are proinflammatory, whilst current data suggest that they may have neuroprotective properties as well. This review provides an overview of the existing recent clinical studies with respect to the role of omega-3 and omega-6 PUFAs as therapeutic agents in chronic, inflammatory, autoimmune neurodegenerative diseases as well as the dosages and the period used for testing.

Keywords: Alzheimer’s disease; EPA/DHA/LA/GLA; Huntington’s disease; PUFA; Parkinson’s disease; amyotrophic lateral sclerosis; clinical trials; multiple sclerosis; omega-3; omega-6; polyunsaturated.

Figure 1

Pathway of biosynthesis of eicosanoids from arachidonic acid. Eicosanoids are not stored within cells and are synthesized as needed when their biosynthesis is activated by trauma/inflammation or cytokines which activate phospholipase A2 (PLA2). Fatty acids that are cleaved by PLA2 from cell membranes are then oxygenated by one of three different families of enzymes to produce eicosanoids [18].

Figure 2

The bidirectional links between inflammation and oxidative stress. Reactive oxygen species (ROS) can act as inflammatory trigger initiating inflammation. On the other hand, inflammation induces oxidative stress. IkB, inhibitory subunit of NFkB; MAPK, mitogen-activated protein kinase; NFkB, nuclear factor kappa-light-chain-enhancer of activated B cells; P, phosphate; ROS, reactive oxygen species [19].

Figure 3

Space filling chemical structures of omega-3 and omega-6 PUFAs.

Figure 4

Pathway of metabolic interconversion of omega-6 and omega-3 polyunsaturated fatty acids. LA and ALA are the parent PUFAs for omega-6 and omega-3, respectively. Abbreviation used: Δ, delta [22].