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Stress takes its toll in Parkinson's disease

Date:
November 11, 2010
Source:
Northwestern University
Summary:
A stressful lifestyle could lead to the premature death of a group of neurons, whose loss triggers the symptoms of Parkinson's disease, according to a new study. Isradipine, a drug already approved for human use by the FDA, has been shown in preclinical studies to reduce the stress on these neurons and rejuvenate them. Scientists currently are conducting a clinical trial to find out if isradipine can be used safely and is tolerated by patients with Parkinson's.

We all know that living a stressful lifestyle can take its toll, making us age faster and making us more susceptible to the cold going around the office.

The same appears to be true of neurons in the brain. According to a new Northwestern Medicine study published Nov. 10 in the journal Nature, dopamine-releasing neurons in a region of the brain called the substantia nigra lead a lifestyle that requires 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, 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 a drug already approved for human use. 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.

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 by the Food and Drug Administration for treatment of high blood pressure.

Parkinson's disease is the second most common neurodegenerative disease in the United States, second only to Alzheimer's disease. The average age of diagnosis is near 60. More than 1 million Americans currently have Parkinson's disease, and this number is rising as the population ages. The symptoms of Parkinson's disease include rigidity, slowness of movement and tremors. No treatment currently is known to prevent or slow the progression of Parkinson's disease.

Although most cases of Parkinson's disease have no known genetic link, Surmeier's study in mice showed that the mitochondrial stress in dopamine-releasing neurons was worsened in a genetic model of early-onset Parkinson's disease, suggesting a similar mechanism in rare familial forms of the disease and the more common forms.

Everyone loses dopamine-releasing neurons with age, Surmeier noted. "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 disease, the hope is that this drug can slow disease progression, giving symptomatic therapies a broader window in which to work."

The study was supported by the National Institutes of Health, United States Department of Defense, Thomas Hartman Foundation For Parkinson's Research, Inc., The Picower Foundation and Dr. Ralph and Marian Falk Medical Research Trust.


Story Source:

The above story is based on materials provided by Northwestern University. The original article was written by Marla Paul. Note: Materials may be edited for content and length.


Journal Reference:

  1. Jaime N. Guzman, Javier Sanchez-Padilla, David Wokosin, Jyothisri Kondapalli, Ema Ilijic, Paul T. Schumacker, D. James Surmeier. Oxidant stress evoked by pacemaking in dopaminergic neurons is attenuated by DJ-1. Nature, 10 November 2010 DOI: 10.1038/nature09536

Cite This Page:

Northwestern University. "Stress takes its toll in Parkinson's disease." ScienceDaily. ScienceDaily, 11 November 2010. <www.sciencedaily.com/releases/2010/11/101110131202.htm>.
Northwestern University. (2010, November 11). Stress takes its toll in Parkinson's disease. ScienceDaily. Retrieved August 1, 2014 from www.sciencedaily.com/releases/2010/11/101110131202.htm
Northwestern University. "Stress takes its toll in Parkinson's disease." ScienceDaily. www.sciencedaily.com/releases/2010/11/101110131202.htm (accessed August 1, 2014).

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