Animal models of Parkinson's disease

Animal models are important tools in experimental medical science to better understand pathogenesis of human diseases. Once developed, these models can be exploited to test therapeutic approaches for treating functional disturbances observed in the disease of interest. On the basis of experimental and clinical findings, Parkinson's disease (PD) was the first neurological disease to be modeled and, subsequently, to be treated by neurotransmitter replacement therapy. Agents that selectively disrupt or destroy catecholaminergic systems, such as reserpine, methamphetamine, 6-hydroxydopamine and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine have been used to develop PD models. Recently, it has been found that agricultural chemicals, such as rotenone and paraquat, when administered systemically, can reproduce specific features of PD in rodents, apparently via oxidative damage. Transgenic animals that over-express a-synuclein are used to study the role of this protein in dopaminergic degeneration. This review critically discusses animal models of PD and compares them with characteristics of the human disease. (C) 2002 Wiley Periodicals, Inc.