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Researchers take aim at causes of Parkinson's disease

Michael Lee, Ph.D. (Photo: Scott Streble)

University of Minnesota scientists hope that two new studies will enhance understanding of the underlying causes of Parkinson’s disease, potentially leading to the development of new drug therapies and treatment options for patients.

In one study, neuroscientist Michael Lee, Ph.D., and his colleagues examined one of the obvious causes of the progression of Parkinson’s: dying neurons in the patient’s brain.

In the lab, researchers discovered a protein called alpha-synuclein with the potential to build up in the endoplasmic reticulum, the part of a neuron responsible for producing dopamine. Accumulation of alpha-synuclein can disrupt the neuron’s functioning, and the cell eventually dies.

Aiming to confirm their previous finding, Lee’s team in another study identified the mechanism behind the death of the cells. When they therapeutically targeted this pathway, they saw a delay in the progression of Parkinson’s disease in an animal model.

“Ultimately, our initial study looks to reduce the stress placed on the endoplasmic reticulum, which we believe would delay the onset and/ or progression of PD,” says Lee, who was the lead investigator of both studies. “In our second study, we … put [our hypothesis] to the test in animal studies. We treated mice and rats with the compound Salubrinal, which alleviates stress in the endoplasmic reticulum and decreases the number of neuron cells that die.”

The mice treated with Salubrinal were significantly healthier and lived longer than those that received a placebo, he says.

Lee says this knowledge will inform future research on how other compounds like Salubrinal could be made more effective and usable in humans to one day treat Parkinson’s disease.

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