ABSTRACT
Parkinson’s disease (PD) is a neurodegenerative disorder characterized mainly by a progressive loss of dopaminergic neurons of the substantia nigra pars compacta. The changes consist of gross and microscopic neuronal depigmentation, neuronal loss, extracellular melanin, and accumulation of iron and Lewy bodies in the remaining neurons (1). One of the major breakthroughs in the understanding of the pathophysiology of PD in the twentieth century was the discovery of a marked reduction in the neurotransmitter dopamine in the striatum of affected patients and the correlation between this loss and the clinical characteristics, i.e., rigidity, tremor, and bradykinesia. It is now recognized that a repertoire of other neurotransmitters (glutamate, noradrenaline, serotonin) is involved in the functional anatomy of the basal ganglia and might interact with or balance dopaminergic neurotransmission. Dopamine is synthesized in the brain from the amino acid L-tyrosine, which is converted to L-3, 4-dihydroxyphenylalanine (Ldopa), the precursor of dopamine via the rate-limiting enzyme tyrosine hydroxylase. Dopamine is stored in vesicles and is transported by a carrier-mediated transport system against a concentration gradient. Under physiological conditions, dopamine is continuously released into the synaptic cleft and activates the postsynaptic receptors. It is returned to the dopaminergic terminals by a carrier-mediated reuptake system and sequestered in the synaptic vesicles for reuse. Dopamine is enzymatically inactivated by the action of mitochondrial monoamine oxidase (MAO) and catechol-O-methyltransferase (COMT), which are localized primarily in glial cells.
