Preferential Extracellular Generation of the Active Parkinsonian Toxin MPP+ by Transporter-Independent Export of the Intermediate MPDP+.

ABSTRACT:

Aims

1-Methyl-4-phenyl-tetrahydropyridine (MPTP) is among the most widely used neurotoxins for inducing experimental parkinsonism. MPTP causes parkinsonian symptoms in mice, primates, and humans by killing a subpopulation of dopaminergic neurons. Extrapolations of data obtained using MPTP-based parkinsonism models to human disease are common; however, the precise mechanism by which MPTP is converted into its active neurotoxic metabolite, 1-methyl-4-phenyl-pyridinium (MPP(+)), has not been fully elucidated. In this study, we aimed to address two unanswered questions related to MPTP toxicology: (1) Why are MPTP-converting astrocytes largely spared from toxicity? (2) How does MPP(+) reach the extracellular space?

Results

In MPTP-treated astrocytes, we discovered that the membra

SUBMITTER: Schildknecht S 

PROVIDER: S-EPMC4649766 | biostudies-literature | 2015 Nov

REPOSITORIES: biostudies-literature