Multiple Antioxidants in the Prevention and Treatment of Parkinson’s Disease

Abstract

Parkinson’s disease (PD) is one of the major progressive neurological disorders for which no preventative or long-term effective treatment strategies are available. Epidemiologic studies have failed to identify specific environmental, dietary or lifestyle risk factors for PD except for toxic exposure to manganese, meperidine (Demerol®, the “designer drug” version of which often contains a toxic byproduct of the synthesis, 1-methyl-4-phenyl 1,2,3,6 tetrahydropyridine [MPTP]), and some herbicides and pesticides. The search for genetic risk factors such as mutation, overexpression or underexpression of nuclear genes in DA neurons in idiopathic PD has not been successful as yet. Polymorphism in certain genes appears to be a risk factor, but there is no direct evidence for the causal relationship between polymorphism and increased risk of PD. In familial PD, mutation in the α-synuclein gene is associated with the disease, but a direct role of this gene in degeneration of DA neurons remains to be established. Although mutations in the Parkin gene has been associated with autosomal recessive juvenile Parkinson’s disease, the role of this gene mutation in causing degeneration of DA neurons has not been defined. We have reported that in hereditary PD, a mutation in the α-synuclein gene may increase the sensitivity of DA neurons to neurotoxins. We hypothesize that, in idiopathic PD, epigenetic (mitochondria, membranes, protein modifications) rather than genetic events are primary targets which, when impaired, initiate degeneration in DA neurons, eventually leading to cell death. Although the nature of neurotoxins that cause degeneration in DA neurons in PD is not well understood, oxidative stress is one of the intermediary risk factors that could initiate and/or promote degeneration of DA neurons. Therefore, supplementation with antioxidants may prevent or reduce the rate of progression of this disease. Supplementation with multiple antioxidants at appropriate doses is essential because various types of free radicals are produced, antioxidants vary in their ability to quench different free radicals and cellular environments vary with respect to their lipid and aqueous phases. L-dihydroxyphenylalanine (L-dopa) is one of the agents used in the treatment of PD. Since L-dopa is known to produce free radicals during its normal metabolism, the combination of L-dopa with high levels of multiple antioxidants may improve the efficacy of L-dopa therapy.

• oxidative stress
• antioxidants
• neurodegeneration
• prevention
• Parkinson’s disease

Key teaching points:

• Free radicals from diverse groups of neurotoxins are a common intermediary risk factor for Parkinson’s disease.

• Multiple antioxidants can reduce the risk of Parkinson’s disease among a high risk population.

• Multiple antioxidants can enhance the efficacy of standard therapy in the treatment of Parkinson’s disease.

• Epigenetic components of neurons (mitochondria, membrane and membrane structures, protein modifications) are primary targets for the action of neurotoxins.

Key teaching points:

• Free radicals from diverse groups of neurotoxins are a common intermediary risk factor for Parkinson’s disease.

• Multiple antioxidants can reduce the risk of Parkinson’s disease among a high risk population.

• Multiple antioxidants can enhance the efficacy of standard therapy in the treatment of Parkinson’s disease.

• Epigenetic components of neurons (mitochondria, membrane and membrane structures, protein modifications) are primary targets for the action of neurotoxins.

This study was supported by U.S. Public Health Service grants RO1 NS 29982 and RO1 NS 35348.