Neurochemistry of Nigral Degeneration

Progressive degeneration of the dopaminergic neurons of the substantia nigra is the pathological hallmark of idiopathic Parkinson’s disease (PD). Based on cytoarchitectonics and melanization, Hassler divided the human substantia nigra into many subsections and demonstrated that the ventral and lateral regions of the substantia nigra may be preferentially involved in early stages of the disease (1,2) (Fig. 1), an observation that was later confirmed in human PD (3,4). The etiology of the progressive degeneration of the substantia nigra pars compacta cells is unknown. It has been proposed that the clinical signs and symptoms of PD emerge only after a loss of 75% of the nigral neurons. Positron emission tomography (PET) and single photon emission computed tomography (SPECT) studies also indicate that the rate of loss of dopaminergic neurons is about 6–13% in patients with PD compared to 0–2.5% in healthy controls (5). These facts suggest that the process of degeneration of nigral neurons is initiated several years ahead of the onset of the clinical expression of the disease. Epidemiological evidence emphasizes the role of environmental toxins in the development of PD. Discoveries of gene mutations responsible for