Chapter 3 -- Current Status, Gaps, and Weaknesses of the Mechanism of Selective Dopaminergic Toxicity of MPTP/MPP+

Abstract

Among Parkinson's disease (PD) toxin models, MPTP/MPP+ has been the most popular, extensively characterized, and widely used to identify the cellular mechanisms associated with the selective degeneration of dopaminergic neurons in PD. A number of recent studies have found some gaps and weaknesses in the generally accepted mechanism especially with regard to the selective dopaminergic toxicity of the model. Accumulating evidence suggests that the inherent physiological predisposition of dopaminergic neurons to generate high oxidative stress, especially when exposed to various environmental and genetic factors and their inability to cope with these conditions effectively, could contribute to their selective destruction. However, the current models for the selective dopaminergic toxicity of MPTP/MPP+ have not taken into account the unique susceptibilities of these neurons. The focus of this chapter is to discuss the discovery, current status, gaps, and weaknesses of the mechanism of the specific dopaminergic toxicity of the MPTP/MPP+ model.