Molecular neurotoxicological models of Parkinsonism: focus on genetic manipulation of mice

Parkinson's disease is a neurodegenerative disorder that affects mainly the nigrostriatal doparminergic system in humans. Several propositions have been put forward to explain the cellular and molecular pathobiology of this syndrome. Initial attempts were made through the use of various agents to manipulate the deleterious effects of toxins that destroy dopaminergic cells both in vitro and in vivo. These studies led to the idea that oxidative stress is an important factor in killing these cells. More recent attempts have made use of genetically modified mice to eliminate or over-express genes of interest. These experiments have suggested that the destruction of dopaminergic cells might be the result of the convergence of dependent and independent molecular pathways and that trigger cellular events might lead to the demise of these doparninergic cells. (C) 2001 Published by Elsevier Science Ltd.