Paraquat (N,N'-dimethyl-4-4'-bipyridium dichloride) is a pesticide analog of MPP+ and etiologically linked to parkinsonism through epidemiological studies (115-117). Paraquat acts to induce oxidative stress by interfering with mitochondria electron transport, especially in the more vulnerable nigrostriatal dopaminergic neurons with a mechanism different from rotenone and MPP+ (118-120). Acute exposure can result in extensive brain damage and death in humans without specific parkinsonian-like pathology (121,122). However, more chronic exposures in rodents (over 24 weeks) can manifest with many features due to dopaminergic dysfunction, including selective loss of nigrostriatal dopaminergic neurons and motor deficits (123,124). Therefore, paraquat, as well as a number of other related reagents, including other pesticides, may replicate features of human parkinsonism when administered in chronic but not acute delivery regimens most likely due to specific uptake and poisoning of nigrostriatal dopaminergic neurons. Paraquat-induced models have similar limitations as rotenone models, but due to issues of specificity and technical issues, this model has not achieved wide usage beyond studies in cell culture and limited animal studies.
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