OXIDATIVE STRESS AND ANTIOXIDANT THERAPY IN PARKINSONS-DISEASE

Parkinson's disease, known also as striatal dopamine deficiency syndro me, is a degenerative disorder of the central nervous system character ized by akinesia, muscular rigidity, tremor at rest, and postural abno rmalities. In early stages of parkinsonism, there appears to be a comp ensatory increase in the number of dopamine receptors to accommodate t he initial loss of dopamine neurons. As the disease progresses, the nu mber of dopamine receptors decreases, apparently due to the concomitan t degeneration of dopamine target sites on striatal neurons. The loss of dopaminergic neurons in Parkinson's disease results in enhanced met abolism of dopamine, augmenting the formation of H2O3, thus leading to generation of highly neurotoxic hydroxyl radicals (OH .). The generat ion of free radicals can also be produced by 6-hydroxydopamine or MPTP which destroys striatal dopaminergic neurons causing parkinsonism in experimental animals as well as human beings. Studies of the substanti a nigra after death in Parkinson's disease have suggested the presence of oxidative stress and depletion of reduced glutathione; a high leve l of total iron with reduced level of ferritin; and deficiency of mito chondrial complex I. New approaches designed to attenuate the effects of oxidative stress and to provide neuroprotection of striatal dopamin ergic neurons in Parkinson's disease include blocking dopamine transpo rter by mazindol, blocking NMDA receptors by dizocilpine maleate, enha ncing the survival of neurons by giving brain-derived neurotrophic fac tors, providing antioxidants such as vitamin E, or inhibiting monoamin e oxidase B (MAO-B) by selegiline. Among all of these experimental the rapeutic refinements, the use of selegiline has been most successful i n that it has been shown that selegiline may have a neurotrophic facto r-like action rescuing striatal neurons and prolonging the survival of patients with Parkinson's disease.