The emerging role of eicosapentaenoic acid in Parkinson’s Disease


 

Parkinson’s disease is a chronic neurological condition that affects the way the brain co-ordinates body movements. Whilst there is no specific test to conclusively show Parkinson’s disease, diagnosis is based on symptoms, medical history and clinical examination. Symptoms, including tremor, rigidity and slowness of movement, result from insufficient formation and action of dopamine, a neurotransmitter that plays a vital role in co-ordinating movement. When about 80% of the dopamine has been lost, the symptoms of Parkinson’s appear, with dopamine levels continuing to fall slowly over many years. Pathologically, the disease is characterised by the accumulation of a protein called alpha-synuclein which forms invasive inclusions called Lewy bodies. Currently the disease is believed to affect around 120,000 people in the UK and, with no cure, available treatments are aimed primarily at helping to control symptoms.

Whilst pharmaceutical intervention in Parkinson’s relates to raising dopamine levels, the role of diet, and specifically dietary fat, within the treatment regime may have profound implications for improving the quality of life in individuals with the disease. Considering that the human brain containsabout 10 billion nerve cells, all of which are encased by a delicate layer of fatty acids (the ‘myelin sheath’) that provides insulation to the cell allowing efficient chemical signalling, it is not surprising that epidemiological data shows a clear relationship between dietary fat intake and the risk of Parkinsons’s disease.1 It is well established that disruption of the myelin sheath results in ‘short wiring’, damage and eventual death of neurons. Whilst the exact mechanisms underlying the process in which the dopamine producing neurons die are unclear, it is likely that oxidative stress, inflammation, and mitochondrial dysfunction may play a large role. In relation to this, increasing evidence suggests an important role for omega−3 and omega−6 polyunsaturated fatty acids in the pathology and therapy of Parkinson’s disease and other neurodegenerative disorders, such as Alzheimer’s disease and Huntington’s chorea.However, because of the high concentration of polyunsaturated fatty acids in the brain, reactive products of lipid peroxidation are likely contributors to neurodegeneration.2 Increased intake of omega−6 fatty acids are known to increase risk of inflammatory disorders whilst, in contrast, the protective effects of omega−3 EPA and DHA supplementation have been demonstrated in experimental animal models of Parkinson’s disease . It is well established that DHA is the primary structural omega-3 in the brain, and it is therefore important to prevent DHA loss. However, because DHA is the most unstable of the long chain omega-3’s, the products of lipid peroxidation derived from DHA supplementation may actually counteract the advantage of DHA in protection against Parkinson’s disease. In contrast, EPA levels within the brain are low in comparison to that of DHA, but this fatty acid plays an important neuroactive role and may have benefits over DHA in treating Parkinson’s disease. Firstly, EPA is a natural precursor to the synthesis of DHA and also blocks the production of an enzyme called PLA2, which releases DHA from cell membranes. By blocking this enzyme, EPA therefore helps to maintain cell membrane integrity within the brain. EPA is also a potent anti-inflammatory, and, unlike DHA, can directly inhibit the production of inflammatory products from the omega-6 arachidonic acid, which themselves are known to contribute to the progression of Parkinson’s. EPA, again preferentially over DHA, is also involved in myelinogenesis by stimulating the production of several myelin proteins which are thought to be key to the inhibition of loss of myelin and therefore brain atrophy.3,4 More recently, EPA has been suggested to regulate dopamine turnover and down-regulate genes involved in neuronal cell death pathways, thus further supporting a beneficial role for ethyl-EPA supplementation as both a preventative and therapeutic tool in neurodegenerative disorders.5

1. Miyake, Y. et al. Dietary fat intake and risk of Parkinson’s disease: a case-control study in Japan. J. Neurol. Sci 288, 117-122 (2010).

2. Liu, X., Yamada, N., Maruyama, W. & Osawa, T. Formation of dopamine adducts derived from brain polyunsaturated fatty acids: mechanism for Parkinson disease. J. Biol. Chem 283, 34887-34895 (2008).

3. Salvati, S. et al. Eicosapentaenoic acid stimulates the expression of myelin proteins in rat brain. J. Neurosci. Res 86, 776-784 (2008).

4. Salvati, S. et al. Stimulation of myelin proteolipid protein gene expression by eicosapentaenoic acid in C6 glioma cells. Neurochem. Int 44, 331-338 (2004).

5. Meng, Q. et al. Ethyl-eicosapentaenoate modulates changes in neurochemistry and brain lipids induced by parkinsonian neurotoxin 1-methyl-4-phenylpyridinium in mouse brain slices. Eur. J. Pharmacol 649, 127-134 (2010).

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