MPTP model

COMMENT I would like to know why you thought the amphetamine model of dopamine neurotoxicity might be more suitable or more revealing for the study of Parkinson s disease than the MPTP model. 

I have argued in the past that looking further at amphetamine toxicity in terms of understanding the mechanism by which those neurons die, might be more revealing. That is not to belittle the importance of MPTP as a model of Parkinson s disease. Certainly in terms of effects in the MPTP-treated monkeys, these animals are of unquestioned value. But in terms of the mechanism by which the neurons die, that was the point that I was questioning, whether the MPTP model would mimic as well as the amphetamine model. 

Wichmann, T., Bergman, H., and DeLong, M.R. (1994) The primate subthalamic nucleus. III. Changes in motor behavior and neuronal activity in the internal pallidum induced by subthalamic inactivation in the MPTP model of parkinsonism. / Neurophysiol 72 521-530. 

Kim H, Jhoo W, Shin E, Bing G (2000b) Selenium deficiency potentiates methamphetamine-induced nigral neuronal loss comparison with MPTP model. Brain Res 862 241-252. 

Although the MPTP model is nearly perfect once developed, it is a toxic model that occurs suddenly after the introduction of the toxin, whereas PD is a progressive disease. Nevertheless the elucidation of the action of MPTP on the mitochondrial respiratory chain, more precisely on the step between I and II has led to the search to the search for agents with neuroprotective abilities in the mitochondrial respiratory chain. 

Du Y Ma Z, Lin S, Dodel RC, Gao F, Bales BCR, Triarhou LC, Cher-net E, Perry KW, Nelson DL, Luecke S, Phebus LA, Bymaster FP, Paul SM (2001) Minocycline prevents nigrostiiatal dopaminergic neurodegeneration in the MPTP model of Parkinson s disease. Proc Natl Acad Sci USA 98 14669-14674. 

Libera tore G, Jackson-Lewis V, Vukosavic S, Mandir AS, Vila M, McAuliffe WJ, Dawson VL, Dawson TM, Przedborski S (1999) Inducible nitric oxide synthase stimulates dopaminergic neurodegeneration in the MPTP model of Parkinson disease. Nat Med 5 1403-1409. 

JNK activation has also been implicated in dopamine neuron death in experimental models of Parkinson s disease. It is therefore not surprising that overexpression of XIAP is also neuroprotective in the MPTP model of Parkinson s disease whereas small molecule inhibitors of kinases that activate JNK have been shown to be effective in numerous models of Parkinson s disease and stroke. Despite these encouraging results, a compound... 

GMl, an agent that prevents delayed excitotoxic cell damage in culture (DeErasquin et al., 1990), attenuates the motor symptoms in primates treated with MPTP (Schneider et al., 1992). In the MPTP model, interest has also centered on the ability of... 

MPTP modei of Parkinsonism In vivo poly-ADP-ribosyiation of p53 in MPTP model of Parkinsonism serves to stabilize p53 and alters its transactivation of downstream genes. 35... 

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