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

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Authors
Wimalasena, Kandatege
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Issue Date
2017
Type
Book chapter
Keywords
Neurotoxic tetrahydro-β-carbolinesComplex I inhibitionReactive oxygen speciesDopamineDopamine transporterVesicular monoamine transporterMonoamine oxidase , Parkinson's disease , MPTP/MPP+ PD model , Neurotoxic tetrahydroisoquinolines , Neurotoxic tetrahydro-β-carbolines , Complex I inhibition , Reactive oxygen species , Dopamine , Dopamine transporter , Vesicular monoamine transporter , Monoamine oxidase
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Wimalasena, Kandatege. 2017. Current Status, Gaps, and Weaknesses of the Mechanism of Selective Dopaminergic Toxicity of MPTP/MPP+. In: Advances in Molecular Toxicology, vol. 11:pp 81-122
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.

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Publisher
Elsevier
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Advances in Molecular Toxicology;v.11
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DOI
ISSN
1872-0854
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