Cell death induced by MPTP, a substrate for monoamine oxidase B

MPTP is known to cause PD symptoms in primates and in rodents. In order to exert its neurotoxicity MPTP must be converted by monoamine oxidase B into MPP+ which is the true toxic agent. MPP+ is taken up by the dopaminergic ne urons of the substantia nigra in which it induces cell death. The present w ork reviews and discusses papers in which specific methods were used to det ermine whether cell death induced by MPTP/MPP+ should be considered as apop tosis or necrosis. These two cell death modes may be distinguished using mo rphological and biochemical criteria. The effect of MPTP/MPP+ was studied i n vitro and in vivo. The results show that no univocal answer is possible. The most widespread interpretation is that MPTP/MPP+ causes apoptosis when its neurotoxic effect is only sligh and necrosis when it is stronger. Simil ar considerations may be made also concerning the type of cell death occurr ing in the dopaminergic neurons in the substantia nigra of PD patients. (C) 2000 Elsevier Science ireland Ltd. All rights reserved.