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Sentry Enzyme Blocks Two Paths to Parkinson’s Diseas

t of Developmental Neurobiology at St. Jude. “In the future, treatments that increase GST pi levels in the substantia nigra might help to prevent or delay the onset of Parkinson’s disease or reduce its severity,” said Smeyne, the report’s senior author.

GST pi is one of a family of similar enzymes that eliminate free radicals generated by pesticides and other chemicals. Two members of this family are present in the brain, but only one of them, GST pi, is found in the dopaminergic neurons of the substantia nigra. Free radicals are highly unstable molecules that readily interact with other molecules, causing cell damage.

The study sheds light on the cause of most cases of Parkinson’s disease, which currently are unexplained. “The majority of these cases of Parkinson’s disease appear to arise because individuals who have a genetic susceptibility to the disease are exposed to environmental toxins such as pesticides and herbicides, which trigger the formation of free radicals that kill dopaminergic neurons in the substantia nigra,” Smeyne said. “We also know that GST pi blocks the process of cell suicide triggered by stresses that the cell can’t overcome, such as an increase in the presence of free radicals or a loss of the cell’s ability to produce energy.”

Smeyne’s team showed that of the two known types of GST in the brain, only GST pi was present in the dopaminergic neurons that are lost in Parkinson’s disease. The scientists then treated two different populations of mice with MPTP, a chemical that causes loss of these cells, in order to determine if levels of GST pi changed. In mice known to be sensitive to MPTP, there was a complete but transient loss of GST pi in the dopaminergic neurons of the substantia nigra, while the same area of the brain in MPTP-resistant mice never completely lost GST pi and recovered their original levels within 12 hours.

In addition, the team showed that when MPTP-resistant mice were trea
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