Converging evidence in support of omega-3 polyunsaturated fatty acids as a potential therapy for Huntington's disease symptoms

Abstract

Huntington's disease (HD) is a genetic, inexorably fatal neurodegenerative disease. Patient average survivability is up to 20 years after the onset of symptoms. Those who suffer from the disease manifest motor, cognitive, and psychiatric impairments. There is indirect evidence suggesting that omega-3 polyunsaturated fatty acids (ω-3 PUFA) could have alleviating effects on most of HD symptoms. These include beneficial effects against cachexia and weight loss, decrease of cognitive impairment over time, and improvement of psychiatric symptoms such as depression and irritability. Furthermore, there is a positive correlation between consumption of ω-3 PUFAs in diets and prevalence of HD, as well as direct effects on the disease via release of serotonin. Unfortunately, to date, very few studies have examined the effects of ω-3 PUFAs in HD, both on the symptoms and on disease progression. This paper reviews evidence in the literature suggesting that ω-3 PUFAs can be used in neurodegenerative disorders. This information can be extrapolated to support further research of ω-3 PUFAs and their potential use for HD treatment.

Keywords: Alzheimer’s disease; Huntington’s disease; cognitive impairment; omega-3; polyunsaturated fatty acids.

Figure 1.

The structures of α-Linolenic acid (ALA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are illustrated. ω−3 PUFAs contain multiple carbon-carbon double bonds, with the first double bond located on the third carbon from the omega end (CH₃). The structures always end with a carboxylic acid (COOH).

Figure 2.

Left side shows the effects of Huntington’s Disease on the serotonin reuptake mechanism and the Kynurenine pathway. SERT (serotonin transporter) and indoleamine 2,3-dioxygenase (IDO) levels are increased in HD. SERT is in charge of removing serotonin from the synaptic cleft to terminate transmission. It reuptakes serotonin back into the presynaptic neuron or it removes from the synaptic cleft. An imbalance in SERT leads to abnormally low levels of serotonin as less serotonin is able to bind to the postsynaptic neuron. IDO is an enzyme that increases the production of kynurenine from tryptophan, decreasing the production of serotonin. Right side shows how EPA, a polyunsaturated fatty acid, is able to counter this imbalance. EPA reduces E₂ series prostaglandins, which in turn reduce the amount of serotonin released. EPA is able to increase serotonin release which counters the reduction of available serotonin to bind to the postsynaptic neuron.