title: Antioxidant therapy in Parkinson's disease.
abstract: It is postulated that endogenous oxidative mechanisms are a major factor in the continuing death of dopaminergic neurons and the progression of Parkinson's disease. Scientific evidence in support of, and negating, the free radical auto-toxicity and dopamine toxicity concepts is reviewed. There is conflicting evidence whether free radicals are involved in the toxicity of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and attempts to prevent the toxicity of MPTP with antioxidant therapy have had variable results. The oxidation of dopamine by monoamine oxidase produces toxic metabolites however animal studies with high dose longterm levodopa and MPTP have failed to show clear evidence for autoxidation. Firm supportive evidence is obtained from the monoamine oxidase B inhibitor experience which demonstrated a block of the toxicity of MPTP in animals and probable prolongation of the course of human Parkinson's disease. The scientific data available is inconclusive but there is significant hope of retarding progressive catecholaminergic neuron degenerative changes by augmenting the free radical scavenging system with antioxidants (such as Vitamin E) and slowing catecholamine oxidation by monoamine oxidase B inhibition. Careful clinical trials with these agents must be performed.
authors.affiliation: Parkinson's Disease Clinic & Laboratory, Ottawa Civic Hospital, Ontario, Canada.
authors.forename: J D
authors.initials: JD
authors.lastname: Grimes
authors.forename: M N
authors.initials: MN
authors.lastname: Hassan
authors.forename: J
authors.initials: J
authors.lastname: Thakar
mesh_terms: D000375:Aging / Q000378:metabolism; D000975:Antioxidants / Q000627:therapeutic use*; D006801:Humans; D008543:Melanins / Q000378:metabolism; D008995:Monoamine Oxidase / Q000378:metabolism; D009498:Neurotoxins / Q000378:metabolism*; D010300:Parkinson Disease / Q000188:drug therapy* / Q000378:metabolism; D012907:Smoking / Q000009:adverse effects; D014810:Vitamin E / Q000378:metabolism
chemical_list: D000975:Antioxidants; D008543:Melanins; D009498:Neurotoxins; C014121:neuromelanin; D014810:Vitamin E; D008995:Monoamine Oxidase