Microtubule assembly is directly affected by MPP+ in vitro

The microtubular system is emerging as a cell target in neurodegeneration evoked by the Parkinsonism-inducing neurotoxin N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and its toxic metabolite N-methyl-4-phenylpyridinium (MPP+). Looking for a direct effect of the neurotoxin on microtubules, we have undertaken an in vitro study by using microtubule protein purified from bovine brain. We show that MPP+, but not MPTP, modifies the initial rate and the critical concentration of assembly without affecting microtubule ultrastructure. These findings strengthen the hypothesis for the role of microtubules in the transduction of MPP+ neurotoxic effect and, probably, in neuronal cell death. (C) 2001 Academic Press.