Abstract.
Many have hypothesized that cell death in Parkinson’s disease is via apoptosis and, specifically, by the mitochondrial-mediated apoptotic pathway. We tested this hypothesis using a mouse dopaminergic cell line of mesencephalic origin, MN9D, challenged with the Parkinsonism-causing neurotoxin MPP+ (1-methyl-4-phenylpyridinium ion). Apoptosis was the main mode of cell death when the cells were subjected to MPP+ treatment under serum-free conditions for 24 h. Caspase-3 and caspase-9, however, were not activated, thus indicating the existence of alternate or compensatory cell death pathway(s) in dopaminergic neuronal cells. Using caspase inhibitors, we demonstrated that these pathways involve caspase-2, −8, −6 and −7. A time-course study indicated that activation of caspase-2 and −8 occurred upstream of caspase-6 and caspase-7. Upon MPP+ challenge, the apoptosis-inducing factor was translocated from the mitochondria into the MN9D cytosol and nucleus. These results suggest the existence of alternative apoptotic pathways in dopaminergic neurons.
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Received 20 September 2004; received after revision 5 November 2004; accepted 22 November 2004
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Chee, J.L.Y., Guan, X.L., Lee, J.Y. et al. Compensatory caspase activation in MPP+-induced cell death in dopaminergic neurons. CMLS, Cell. Mol. Life Sci. 62, 227–238 (2005). https://doi.org/10.1007/s00018-004-4413-4
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DOI: https://doi.org/10.1007/s00018-004-4413-4