The discovery that MPTP, which is structurally similar to a number of commonly used herbicides and pesticides, can induce specific loss of substantia nigra neurons in many vertebrate species, from humans to mice, has lead to the development of a useful model of Parkinson disease. In mice, MPTP demonstrates differential toxicity that is dependent on the strain of animal examined (Sonsalla and Heikkila 1988; Muthane et al. 1994; Hamre et al. 1999). This finding supports the hypothesis that the loss of substantia nigra neurons in Parkinson disease may result from a genetic sensitivity to a number of environmental agents (Veldman et al. 1998; Stoessl 1999). In a recent study, the chromosomal loci containing the genetic sequences responsible for this sensitivity was identified on the telomeric end of mChr.1 (Cook et al. 2003). Further studies into the genetic and biochemical pathways involved in MPTP toxicity will lead to a better understanding of idiopathic Parkinson disease and provide clues to novel targets for therapeutic interventions.
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