Neuroprotective Effects of MAO-B Inhibition: Clinical Studies in Parkinson’s Disease
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Parkinson’s Disease (PD), characterized by a marked loss of nigrostriatal neurons , is generally a disorder of progressive disability. While additional neuronal systems of the PD brain are altered , the change most closely linked to the clinical symptomatology of Parkinsonism is the impaired generation of striatal dopamine. Dopamine production may also figure in the special vulnerability of substantia nigra pars compacta neurons in PD. Several hypotheses for the decline in dopaminergic neurons have been advanced. One speculation has been that one or more exogenous toxins might produce a metabolic effect damaging these neurons. Several neurotoxins with highly specific actions against nigrostriatal dopaminergic neurons are known. These produce parkinsonian symptomatology both in animal models and, in the case of manganese and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), in man. MPTP has been the most intriguing of these because of its need for conversion in the brain prior to exerting toxicity to nigrostriatal dopamine neurons via their mitochondrial metabolism. The unique properties of MPTP have provided grist for speculation that PD could conceivably be the outcome of intermittent or continuous neurotoxicity from exposure to similar types of compounds [3–5].
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