Biochemistry of Parkinson's disease with special reference to the dopaminergic systems

Abstract

The cardinal neurochemical abnormality in Parkinson's disease is the decreased dopamine content in the striatum, resulting from the loss of dopaminergic neurons in the mesencephalon. Precise analysis of the dopaminergic neurons in the midbrain demonstrates, however, that this cell loss is not uniform. Some dopaminergic cell groups are more vulnerable than others. The degree of cell loss is severe in the substantia nigra pars compacta, intermediate in the ventral tegmental area and cell group A8, but nonexistent in the central gray substance. This heterogeneity provides a good paradigm for analyzing the factors implicated in this differential vulnerability. So far, the neurons that degenerate have been shown to contain neuromelanin, high amounts of iron, and no calbindin28K, and to be poorly protected against oxidative stress. By contrast, the neurons that survive in Parkinson's disease are free of neuromelanin, calbindinD28-positive, contain low amounts of iron, and are better protected against oxidative stress. The analysis of the pattern of cell loss in Parkinson's disease may thus bring new clues as to the mechanism of nerve cell death in Parkinson's disease.