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Organic Cation Transporters pp 205–216Cite as

Organic Cation Transporters as Modulators of Neurodegeneration and Neuroprotection in the Brain

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Abstract

The organic cation transporters have emerged as important regulators in human health and diseases. This chapter will discuss the latest studies demonstrating how a sub-group of these transporters, the organic cation transporter-3 (OCT3), would modulate neurodegeneration and neuroprotection in the brain. These roles of OCT3 have been documented in the dopaminegic nigrostriatal system, a pathway that is affected in Parkinson’s disease (PD). Three experimental models of nigrostriatal neurotoxicity will be discussed to illustrate how OCT3 modulate cell viability. In the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP, previously discovered to cause parkinsonism in a group of drug addicts) mouse model, blocking OCT3 function is neuroprotective. However, OCT3 deletion enhances neurotoxicity in the paraquat (a herbicide that increases the risk of developing PD) and methamphetamine mouse models. These observations are consistent with the ability of OCT3 to bi-directionally transport these toxins and consistent with the expression pattern of OCT3 in the brain. Polymorphisms of OCT3 have been reported in humans and this transporter is suggested to be a susceptibility gene contributing to PD.

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Authors and Affiliations

  1. Department of Clinical Neurobiology, Institute of Translational and Stratified Medicine, Plymouth University, The John Bull Building, Plymouth, PL6 8BU, UK

    Kim Tieu Ph.D.

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Correspondence to Kim Tieu Ph.D. .

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Editors and Affiliations

  1. Experimental Nephrology, MC D, University of Münste, Münster, Nordrhein-Westfalen, Germany

    Giuliano Ciarimboli

  2. CNRS UMR8246/Inserm U1130/UPMC UMCR18/Sorbonne University, Neuroscience Institute of Biology Paris-Seine, Paris, France

    Sophie Gautron

  3. Experimental Nephrology, MC D, University Hospital Münste, Münster, Nordrhein-Westfalen, Germany

    Eberhard Schlatter

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Tieu, K. (2016). Organic Cation Transporters as Modulators of Neurodegeneration and Neuroprotection in the Brain. In: Ciarimboli, G., Gautron, S., Schlatter, E. (eds) Organic Cation Transporters. Springer, Cham. https://doi.org/10.1007/978-3-319-23793-0_8

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