Role of heat shock proteins in MPTP-induced neurotoxicity.

1. MPTP and its major metabolite MPP+ have significant effects on body temperature regulation in mice, which are both age and strain dependent. 2. These effects were produced by intraperitoneal injection of either MPTP or MPP+ suggesting that the predominant site of action lies outside the blood-brain barrier. 3. The initial hyperthermia induced in CD-1 mice, which was sufficient to lead to the induction of HSP 72, appears to have a protective effect with regard to striatal dopamine depletion. 4. Cultured CHO cells are sensitive to MPP+ cytotoxicity at high concentrations. This toxicity can be reduced by heat shocking the cells prior to the addition of MPP(+)-containing media. 5. In summary, these in vivo and in vitro data strongly suggest that heat shock proteins (HSP 72) play a neuroprotective role in MPTP-induced neurotoxicity.