ABSTRACT
MPTP represents a classical compound that is metabolized within astrocytes to a reactive intermediate, 1-methyl-4-phenylpyridinium ion (MPP+) with subsequent propensity to selectively destroy nigrostriatal dopaminergic neurons (Burns et al., 1983; Heikkila et al., 1984; Langston et al., 1984).
The fully oxidized pyridinium metabolite (MPP+) is likely to be the mediator of MPTP neurotoxicity and is apparently able to damage neuronal cells after being formed within and released from astrocytes (Di Monte et al., 1996). Of note is that MPP+, despite its changed chemical structure, can cross the plasma membrane into the extracellular space after being formed within astrocytes (Di Monte et al., 1992a). Furthermore, there is some evidence that MPP+ can also be formed extracellularly, presumably via autoxidation of the 1-methyl-4-phenyl-2,3-dihydropyridinium intermediate (MPDP+), after this latter compound has been generated within astrocytes and has crossed astrocyte membranes (Di Monte et al., 1992a) (Figure 27.1).
