Mayo scientist one of 11 to receive grant from Michael J. Fox Foundation for Parkinson's Research

Thursday, January 23, 2003

JACKSONVILLE, Fla., Jan. 23, 2003 — The Michael J. Fox Foundation for Parkinson's Research awarded Leonard Petrucelli, Ph.D., a neuroscientist at Mayo Clinic in Jacksonville, a $375,000 grant to study the role of protein degradation in Parkinson's disease. Petrucelli was one of 11 awardees around the world to receive grants totaling about $2.6 million under this initiative. He will study the impact of abnormal protein accumulation associated with Parkinson's disease on the function of proteasomes, the cellular structures that break down unwanted proteins.

The hallmark of many neurodegenerative diseases is abnormal protein accumulation. In the case of Parkinson's disease, a protein called alpha-synuclein is the culprit. In several in vitro studies (studies done with cells isolated from living organisms) alpha-synuclein inhibits proteasomes from performing their garbage can-like function. Petrucelli says it's important to confirm that observation in an animal model. "Sometimes experiments carried out in cell culture don't yield the same results in humans," he says. "I wanted a mouse model that provides a mechanism for what's causing this abnormal accumulation."

Petrucelli developed a transgenic mouse that carries a marker for proteasomal activity. He plans to cross breed these mice with transgenic models of neurodegenerative diseases such as Parkinson's disease, which produce abnormal protein deposition in their brains. (Transgenic mice have human pathogenic genes inserted into their DNA so offspring will carry otherwise impossible characteristics or traits.)

In the crossbred mice, under a microscope he will be able to see the marker, indicating proteasomal activity, or the lack of it, as well as in what areas of the brain it occurs. "The marker actually fluoresces green light," Petrucelli says. "The marker normally goes to the proteasome — the garbage can if you will — to get degraded. But if you close the garbage can lid because the abnormal proteins are mucking up the garbage can, that marker can no longer get into the garbage can, so it starts to accumulate. Since it's fluorescent, you're able to see it under a microscope. More green light means more inhibition, which is bad." Not only will researchers be able to see if proteasomes aren't functioning, they'll be able to see where in the brain the dysfunction is occurring.

The ultimate goal of Petrucelli's work is to uncover a mechanism that permits Parkinson's disease to happen so that mechanism can be targeted with drugs that could cure or prevent it. If his research is fruitful, we could see drugs developed to re-enable proteasomes to function in the presence of abnormal protein accumulation or drugs that will act like proteasomes to break down those harmful proteins.

About 1 million Americans, including actor Michael J. Fox, are estimated to suffer from Parkinson's disease, a motor system disorder characterized by tremors, rigidity, slow movement and balance problems.

The Michael J. Fox Foundation for Parkinson's Research is dedicated to ensuring the development of a cure for Parkinson's disease within this decade through an aggressively funded research agenda.

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