Caspase-11 Mediates Inflammatory Dopaminergic Cell Death in the 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine Mouse Model of Parkinson's Disease
Copyright policy )Caspase-11 Mediates Inflammatory Dopaminergic Cell Death in the 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine Mouse Model of Parkinson's Disease
The present study was designed to elucidate the inflammatory and apoptotic mechanisms of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurotoxicity in a model of Parkinson's disease. Our results showed that mutant mice lacking thecaspase-11gene were significantly more resistant to the effects of acute treatment with MPTP than their wild-type mice. Thus, the neurotoxicity of MPTP seems to be mediated by the induction of both mitochondrial dysfunction and free radical generation. Previously, we showed that overexpression of the Apaf-1 dominant-negative inhibitor inhibited the mitochondrial apoptotic cascade in chronic MPTP treatment but not in acute MPTP treatment. The present results indicate that MPTP neurotoxicity may be mediated via activation of the caspase-11 cascade and inflammatory cascade, as well as the mitochondrial apoptotic cascade.
- University of Tokyo Japan
- Juntendo University Japan
- Sapporo Medical University Japan
Mice, Knockout, Neurons, Dopamine, Immunoblotting, Apoptosis, Cell Count, Caspase Inhibitors, Immunohistochemistry, Caspases, Initiator, Mice, Inbred C57BL, Neostriatum, Disease Models, Animal, Mice, 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine, Caspases, Animals, Microglia, Enzyme Inhibitors, Inflammation Mediators, Interleukin-1
Mice, Knockout, Neurons, Dopamine, Immunoblotting, Apoptosis, Cell Count, Caspase Inhibitors, Immunohistochemistry, Caspases, Initiator, Mice, Inbred C57BL, Neostriatum, Disease Models, Animal, Mice, 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine, Caspases, Animals, Microglia, Enzyme Inhibitors, Inflammation Mediators, Interleukin-1
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