Impact of omega-3 fatty acids in Parkinson's disease

doi:10.1016/j.arr.2011.03.001

Ageing Research Reviews

Volume 10, Issue 4, September 2011, Pages 453-463

https://doi.org/10.1016/j.arr.2011.03.001 Get rights and content

Abstract

Current epidemiological, preclinical and clinical data suggest that omega-3 polyunsaturated fatty acids (n-3 PUFAs) may constitute therapeutic strategy for several disorders of the central nervous system, including Parkinson's disease (PD). PD is a neurodegenerative disorder primarily characterized by motor symptoms but which also includes several other pathological features such as autonomic system failures, mood disorders, and cognitive deficits. Current pharmacological options for the disease are limited to symptom management and their long-term use leads to important side effects. In this review, we discuss the evidence for the effects of n-3 PUFAs in PD both from an epidemiological perspective as well as in light of data gathered on various pathological features of the disease. Effects of n-3 PUFAs on the dopaminergic system, α-synucleinopathy, their possible mechanisms of action as well as their therapeutic potential for PD patients are also reviewed. n-3 PUFAs are inexpensive, readily transferable to the clinical setting and their use could represent a neuroprotective strategy or a disease-modifying option to delay the appearance of symptoms. It could also be beneficial as a symptomatologic treatment or serve as an add-on therapy to current pharmacological approaches. Review of the current literature as well as the undertaking of future clinical trials will shed light on these possibilities.

Highlights

► We recently demonstrated the efficacy of omega-3 fatty acids to protect against neuronal cell death in an animal model of Parkinson's disease. ► Our analyses further revealed the implication of the neurotrophic factor BDNF as a mechanism of action underlying the beneficial effects of long-term omega-3 dietary supplementation. ► Studies from various research groups have underscored the effects of omega-3 on various traits of Parkinson's disease, all pointing towards a beneficial role of omega-3 fatty acids.

Introduction

Parkinson's disease (PD) is among the most common neurodegenerative disorders and its prevalence increases with age. Worldwide aging of the population has thus drawn attention to the need for developing therapeutic strategies that could delay the onset of neurodegenerative disorders, or even halt progression of such diseases. Beneficial impacts of omega-3 polyunsaturated fatty acids (n-3 PUFAs) have been reported in a wide range of disorders affecting the central nervous system. Recently, n-3 PUFA effects have been assessed in epidemiological studies as well as in animal models of PD. Although further clinical trials are needed to investigate the impact of n-3 PUFAs for PD patients, epidemiological and preclinical studies have identified low n-3 PUFA consumption as a potential modifiable risk factor for neurodegenerative disorders. This review focuses on the effects of n-3 PUFAs on the underlying pathological processes leading to PD features and how the knowledge collected up to now can be translated into the clinical use of n-3 PUFAs.

Section snippets

Parkinson's disease overview

Typical clinical manifestations include resting tremors, bradykinesia, akinesia, muscular rigidity and postural instability (see for reviews Lang and Lozano, 1998a, Lang and Lozano, 1998b, Schapira and Tolosa, 2010). However, non-motor features, such as sleep abnormalities, autonomic system failures, mood disorders as well as cognitive deficits, are also important components of the clinical expression of PD (Lim and Lang, 2010). To this day, no curative treatment is available and the vast

n-3 PUFAs: description and functions

PUFAs can be divided into distinct families according to the position of the first double bond relative to the terminal methyl group. α-Linolenic (ALA) and linoleic acids constitute the precursors of the n-3 and n-6 PUFA families, respectively, and are essential to humans since they cannot be synthesized de novo. Eicosapentaenoic (EPA) and docosahexaenoic acids (DHA) are two important n-3 PUFAs mainly found in oily fish. Arachidonic acid (ARA) stands as an important n-6 PUFA and a precursor to

Epidemiological and post-mortem studies linking n-3 PUFAs and PD

Epidemiological and post-mortem studies focusing on n-3 PUFAs in PD are rather limited. Nevertheless, evidence accumulated thus far has uncovered a relationship between dietary habits and the incidence of the disease. A prospective follow-up study based on food questionnaires answered by 131,368 participants revealed that adherence to Mediterranean diets, traditionally composed of vegetable, fruit and fish, is associated with a reduced incidence of PD (Gao et al., 2007). This study did not

Motor symptoms

Thus far, no formal clinical assessment of the impact of n-3 PUFAs on motor symptoms in PD patients has been reported. However, the symptomatologic effect of DHA in PD can be extrapolated from studies in monkeys exposed to the neurotoxin MPTP and consequently developing a parkinsonian syndrome. For example, the study of Samadi et al. (2006) was designed to evaluate the potential of high dose of DHA to acutely reduce levodopa-induced dyskinesias (see Section 5.3). As a control, a group of MPTP

Dopaminergic neurotransmission system and dietary n-3 PUFAs

Regulation of the dopaminergic synapse involves the vesicular monoamine transporter 2 (VMAT2) and the dopamine transporter (DAT), which are localized in the synaptic vesicle and plasma membranes, respectively, of the presynaptic compartment. DAT mediates the removal of DA from the synaptic cleft back to the presynaptic component, while VMAT2 is mainly involved in the vesicular storage of monoamines in axon terminals. DA receptors, which are subcategorized into two large families, namely D₁-like

Neuroprotective properties of n-3 PUFAs: evidence from animal studies

It is only recently that the beneficial effects of long-term n-3 PUFA supplementation were demonstrated in rodent models of parkinsonism (Bousquet et al., 2008). More specifically, a 10-month dietary supplementation with n-3 PUFAs protected mice from nigral and striatal dopaminergic-related depletion caused by the administration of the neurotoxin MPTP (Bousquet et al., 2008). Long-term consumption of n-3 PUFAs also blunted MPTP-induced decreases of Nurr1 and DAT mRNA, Nurr1 being a nuclear

Interactions between α-syn and n-3 PUFAs

Lewy bodies are defined as intraneuronal protein aggregates of α-syn and constitute one of the essential neuropathological hallmarks for post-mortem diagnosis of PD. The extensive description of Lewy body distribution by Braak and colleagues (Braak et al., 2003), together with recent data collected in post-mortem studies of transplanted patients where a number of long-term grafted cells express Lewy body disease (Kordower et al., 2008, Li et al., 2008), led to the hypothesis that α-syn could be

Conclusions

PD is a very complex neurodegenerative disorder whose clinical expression includes peripheral, cognitive and motor symptoms. The clinical benefits of levodopa treatment are often short-lived and lead to important motor complications such as dyskinesias. There is a high incentive for seeking alternative therapies and especially neuroprotective agents that would allow interventions at the earliest stages of the disease. Since PD manifests when nigral degeneration has reached more than 50–70%, the

Acknowledgements

This work was supported by the Parkinson Society Canada and CIHR Institute of Nutrition and the Canada Foundation for Innovation (FC and FC). MB is supported by a Vanier Canada Graduate Scholarship from CIHR. The authors would like to thank Dr Richard Poulin for his valuable editing and Mr. Gilles Chabot for his excellent work in graphic images.

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ReviewImpact of omega-3 fatty acids in Parkinson's disease

Abstract

Highlights

Introduction

Section snippets

Parkinson's disease overview

n-3 PUFAs: description and functions

Epidemiological and post-mortem studies linking n-3 PUFAs and PD

Motor symptoms

Dopaminergic neurotransmission system and dietary n-3 PUFAs

Neuroprotective properties of n-3 PUFAs: evidence from animal studies

Interactions between α-syn and n-3 PUFAs

Conclusions

Acknowledgements

Neurosci. Lett.

Cell. Signal.

Lancet Neurol.

Prostaglandins Leukot. Essent. Fatty Acids

Prog. Lipid Res.

Neurochem. Int.

J. Nutr. Biochem.

Prog. Neuropsychopharmacol. Biol. Psychiatry

J. Lipid Res.

Neurobiol. Aging

Prostaglandins Leukot. Essent. Fatty Acids

Prostaglandins Leukot. Essent. Fatty Acids

Prostaglandins Leukot. Essent. Fatty Acids

Neuron

Neurosci. Res.

J. Nutr.

J. Lipid Res.

Toxicol. Lett.

Prog. Neuropsychopharmacol. Biol. Psychiatry

FEBS Lett.

J. Nutr.

Prog. Lipid Res.

J. Affect Disord.

J. Nutr.

Biochim. Biophys. Acta

Biol. Psychiatry

Prostaglandins Leukot. Essent. Fatty Acids

Am. J. Clin. Nutr.

Cell

Neurosci. Lett.

Brain Res. Mol. Brain Res.

Lancet Neurol.

J. Biol. Chem.

Neurobiol. Dis.

FEBS Lett.

Neurochem. Int.

Lancet Neurol.

Neurosci. Lett.

Neurosci. Res.

Lancet

Prostaglandins Leukot. Essent. Fatty Acids

J. Biol. Chem.

J. Lipid Res.

J. Affect. Disord.

Schizophr. Res.

Exp. Neurol.

Life Sci.

Neurosci. Lett.

Neurochem. Int.

A systematic review of prevalence studies of dementia in Parkinson's disease

Mov. Disord.

Review
Impact of omega-3 fatty acids in Parkinson's disease