Parkinson's disease (PD) is one of the most common neurodegenerative disorders. Molecular biological studies have suggested that PD may be caused by multiple etiologies. Mutations of several different genes have been identified to be responsible for the different inherited forms of PD. In many of these instances, the clinical, neurochemical, neuropathological, and pharmacological characteristics bear significant similarities to that of idiopathic PD. With some mutations, the patients also exhibit cerebellar and cortical dysfunctions along with the well-established clinical features commonly noted in idiopathic PD (1).
Although the inherited forms of PD have provided insights into the pathological process underlying PD, they represent only a small fraction of PD cases. Animal models and epidemiological studies point to the possibility that mitochondrial tox-icity induced by environmental toxins could be one cause of PD. One study in a large number of patients who had been exposed to several types of occupational chemicals and pesticides suggested that those patients who have been exposed to pesticides and herbicides had a 70% higher incidence of PD, 10 to 20 years after the original time of exposure, than those who were exposed to most other occupational chemicals (2).
Although there may be multiple causes of PD, the most common denominator among experimentally induced animal models of PD, inherited forms of PD as well as idiopathic PD is the profound degeneration of the dopaminergic neurons of sub-stantia nigra pars compacta (SNpc). The striatum contains 80% of all the dopamine in the brain (3,4). The A9 group of dopaminergic neurons, consisting of densely packed cells in the SNpc, and the A10 group located in the ventral tegmental area of Tsai (VTA) are the major source of dopamine in the brain and, more specifically, the basal ganglia (5,6).
The VTA and SNpc dopamine neurons have unique neurophysiological and neurochemical properties, as well as a unique pattern of ontogenesis (7). Recognizing the neurochemical and molecular factors that are unique to the ventral tier of the SNpc, the site of maximum degeneration in PD, is crucial to the understanding of the pathogenesis of PD.
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