The molecular mechanism or mechanisms of neurodegeneration in PD, the original cause of the selective dopaminergic neuronal loss, are mostly unknown. Many important findings have been reported; however, no unifying and universal theory has been proposed and accepted. The most plausible explanation is that these dopaminergic neurons contain the highest concentration of DA,1which, it is presumed, increases their vulnerability. The DA itself is not toxic at physiologic concentrations. However, it is actively metabolized, primarily by monoamine oxidase, producing toxic derivatives, of which the most damaging are aldehydes. Normally, these derivatives are polymerized to form dark nontoxic neuromelanin, which is deposited in the cells. The earliest pathologic finding related to PD was the depigmentation of the substantial nigra in patients with parkinsonism of infectious origin. In the early 1920s, it was considered improbable that a change in such a tiny area of the brain could cause the dramatic symptoms; as we now know, there are only about 5 × 105pigmented dopaminergic neurons in normal substantia nigra.2The depigmentation probably indicates the decrease in the concentration of DA or the inability of the cells to polymerize its toxic derivatives, or both.