Organic cation transporters as modulators of neurodegeneration and neuroprotection in the brain
Book Chapter
Tieu, K. (2015). Organic cation transporters as modulators of neurodegeneration and neuroprotection in the brain
. 205-216. 10.1007/978-3-319-23793-0_8
Tieu, K. (2015). Organic cation transporters as modulators of neurodegeneration and neuroprotection in the brain
. 205-216. 10.1007/978-3-319-23793-0_8
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.
