Mechanisms of neuronal loss in Parkinson's disease: a neuroanatomical-biochemical perspective.

It is shown that the specific inter- and subregional patterns of striatal dopamine loss in idiopathic Parkinson's disease can serve as a criterion for the evaluation of neurotoxic processes suggested to play an etiological role in this disorder. Based on this premise, the possibility is examined that dopamine-based free radicals (oxidative stress), or a MPTP-like mechanism may be the primary cause of the substantia nigra cell death in idiopathic Parkinson's disease. It is concluded that the most likely determinant of the specific patterns of nigral cell loss and striatal dopamine deficit might be the peculiar topomorphological arrangement of the melanin-containing neurones in the human substantia nigra.