Figure 1

Evolution of PD. During the course of normal aging (green line), small but slow dopaminergic degeneration occurs without any motor symptoms. Typically idiopathic PD (iPD) (blue line) is of unknown origin but is thought to develop gradually over time with a slow degeneration of dopaminergic neurons leading to the emergence of the classic PD motor symptoms later in life. Another model of dopamingeric neurodegeneration leading to PD motor symptoms involves repeated exposure to environmental toxicants over time in combination with a genetic predisposition to dopaminergic neuron loss (yellow line). Early-onset PD (red line), as caused by mutations in the parkin gene, involves a precipitous decline in dopaminergic neuron number where PD motor symptoms can present decades prior to those in iPD. One more scenario (not shown) of PD-motor symptom development involves possible in utero environmental toxicants or genetic factors leading to an atypically low number of dopaminergic neurons at birth and increased susceptibility to PD development.