A University of Rochester team of scientists has received $2 million from the National Institutes of Health to study how environmental agents and genetics might team up to cause Parkinson's disease.
Currently scientists have little understanding of what causes Parkinson's, though there are several drugs and a few surgical procedures to treat the disease, where a tiny group of dopamine-producing neurons deep within the brain die. This nerve cell death leads to the tremors, rigidity, and slow movement that mark the disease as it progresses slowly over a period of years or decades.
The Rochester team, with extensive experience in gene manipulation and environmental toxins, will model how specific genes might interact with various environmental agents. In many diseases, genetic mutations -- what we commonly think of as a family history -- make a person much more vulnerable to get that disease. For instance, someone with colon cancer boosts his or her risk of getting that disease by eating red meat, and someone with heart disease is at greater risk by smoking and living a couch-potato lifestyle. This study is among the first to test whether such a link between environmental toxins and so-called susceptibility genes can produce disease.
The team will first study a gene that enhances the uptake of the toxin MPTP, a chemical that damages dopamine neurons in much the same way as occurs in the brains of Parkinson's patients. The team will check whether having this gene increases sensitivity to MPTP and a close chemical cousin, the herbicide paraquat. A key part of the effort is technology developed at the University to turn on genes in an organism's nervous system precisely when researchers want, enabling them to manipulate specific vulnerability genes involved in Parkinson's disease and to study the impact of toxins on those cells.
The five-year grant goes to a team headed by Howard Federoff, chief of the Division of Molecular Medicine and Gene Therapy and director of the Center on Aging and Developmental Biology. Working with Federoff are Deborah Cory-Slechta, chair of the Department of Environmental Medicine and acting chair of the Department of Neurobiology and Anatomy, and Handy Gelbard and Eric Richfield, associate professors of neurology. Most of the funding will go toward salaries for graduate students, faculty members and other researchers.