Biochemistry Of The Neurotoxic Action Of MPTP And What It May Teach Us About The Etiology Of Idiopathic Parkinsonism

The past four years have been an exciting period in the history of parkinsonian research. Thanks to the efforts of an extraordinary number of investigators who have entered the field and a close interaction among neurologists, pharmacologists, biochemists, cell biologists, and chemists, we have progressed in a short time span from the first report that MPTP causes neurological symptoms close to those seen in Parkinsonism patients to an understanding of the main events leading to nigrostriatal cell death initiated by MPTP. One purpose of this paper is to summarize the biochemical events involved in this process, emphasizing recent, largely unpublished data and pointing out unresolved questions. Our second aim is to give an overview of what is being done to provide evidence for the hypothesis, which is gaining increasing acceptance, that idiopathic Parkinsonism is caused by slow-acting environmental neurotoxins. We will point out the battery of relatively simple in vitro tests for screening such potential neurotoxins and how they may eventually facilitate elimination of the disease. The original studies to be summarized represent, in part, collaboration with our colleagues, A. Trevor and N. Castagnoli at our University and in part, collaboration with Dr. R. Heikkila’s laboratory.