Apoptotic molecules and MPTP-induced cell death.

ABSTRACT

MPTP-induced neurotoxicity is one of the experimental models most commonly used to study the pathogenesis of Parkinson's disease (PD). MPTP administered in vivo to mice causes selective loss of dopaminergic neurons in the substantia nigra (SN), as in this disease. Cell death may be induced in vitro by MPP(+), the active metabolite of MPTP, when neuronal cell cultures are used. Biochemical mechanisms underlying cell death induced by MPTP/MPP(+) still remain to be clarified completely. This article reviews some recent findings linking the effects of MPTP/MPP(+) with molecules typically involved in apoptotic pathways. This type of research has made extensive use of genetically manipulated systems such as transgenic mice and transfected cell lines. Evidence has emerged to suggest that Bcl-2, Bax, JNK, and caspases are implicated in neurotoxic effects due to in vivo MPTP administration to mice. Different neuronal cell lines such as MN9D cells, SH-SY5Y cells, cerebellar granule neurons, cortical neurons, and GH3 cells were also tested to investigate the possible involvement of Bcl-2, Bax, and caspases in in vitro MPP(+)-induced neurotoxicity.