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Stress Takes its Toll in Parkinson’s Disease

We all know that living a stressful lifestyle can take its toll, making us age faster and decreasing our immunity.

The same appears to be true of neurons in the brain. According to a Northwestern Medicine study published November 10 in the journal Nature, dopamine-releasing neurons in a region of the brain called the substantia nigra require lots of energy, creating stress that could lead to the neurons’ premature death. Their death causes Parkinson’s disease.

“Why this small group of neurons dies in Parkinson’s disease is the core question we struggled with,” says lead author D. James Surmeier, PhD, the Nathan Smith Davis Professor and chair of physiology at Northwestern University Feinberg School of Medicine. “Our research provides a potential answer by showing this small group of neurons uses a metabolically expensive strategy to do its job. This “lifestyle’ choice stresses the neurons’ mitochondria and elevates the production of superoxide and free radicals ““ molecules closely linked to aging, cellular dysfunction, and death.”

The good news is preclinical research shows this stress can be controlled with an FDA-approved drug. By preventing calcium entry, the drug isradipine reduced the mitochondrial stress in dopamine-releasing neurons to the levels seen in neurons not affected by the disease.

“By lowering their metabolic stress level, we should be able to make dopamine-releasing neurons live longer and delay the onset of Parkinson’s disease,” he said. “For individuals diagnosed with Parkinson’s, the hope is that this drug can slow progression, giving symptomatic therapies a broader window in which to work.

Northwestern Medicine scientists currently are conducting a clinical trial to find out if isradipine can be used safely and is tolerated by patients with Parkinson’s. Isradipine is already approved for treatment of high blood pressure.