News Summary

• University of Minnesota researchers have recently published updates to two distinct efforts aimed at combatting Parkinson’s disease by tackling the basic science behind the disease. 
• The end goal of the two studies is to advance understanding of the mechanism’s behind the condition’s neurodegeneration. 

Quotes

•  “Ultimately, our initial study looks to reduce the stress placed on the ER, which we believe would delay the onset and/or progression of PD. In our second study, we the alpha-Synuclein hypothesis and put it to the test in animal studies, treating mice and rats with the compound Salubrinal, which alleviates stress in the ER and decreases the number of cells that die.” - Michael Lee, Ph.D., University of Minnesota neuroscientist and lead investigator of both studies 

 

Full Text

MINNEAPOLIS/ST. PAUL (FEB. 29, 2012) – University of Minnesota researchers have recently published updates to two distinct efforts aimed at combatting Parkinson’s disease by tackling the basic science behind the disease.

The end goal of the two studies is to advance understanding of the mechanism’s behind the condition’s neurodegeneration in hopes of developing a drug that will provide effective therapy for PD patients, treating the underlying causes of the disease and other related disorders.

In the first study, U of M researchers seek to find the reasons behind the death of neurons in patients suffering from Parkinson’s disease. One of the most obvious causes of Parkinson’s disease is the death of neurons responsible for synthesizing dopamine, but the direct cause has yet to be discovered.

An important advance in this area has been the evidence supporting the view that a protein called alpha-synuclein can build up in the part of a neuron cell that produces dopamine, the endoplasmic reticulum (ER). The buildup can interfere with the neuron’s normal functioning, eventually leading to the demise of the neurons. The details of just how alpha-synuclein causes neurons to die has been controversial, however.

In their second study, published in the Journal of Neuroscience, U of M researchers identify a mechanism by which alpha-synuclein does indeed kill those neurons, and shows that therapeutic targeting of this pathway can delay disease onset in animal models of Parkinson’s.

Researchers believe the onset of the disease is caused by the death of brain cells that produce dopamine, a chemical messenger that plays an important role in defining motor skill and focus.

“Ultimately, our initial study looks to reduce the stress placed on the ER, which we believe would delay the onset and/or progression of PD,” said U of M neuroscientist Michael Lee, Ph.D., lead investigator of both studies. “In our second study, we the alpha-Synuclein hypothesis and put it to the test in animal studies, treating mice and rats with the compound Salubrinal, which alleviates stress in the ER and decreases the number of cells that die.”

Lee and his colleagues found that mice treated with Salubrinal had an increase in their projected lifespan and the treatment dramatically delayed the onset of PD. The rats who received Salubrinal have been significantly healthier and their bodies functioned for longer periods of time, than those given a placebo.

The combination of these two studies shows that chronic stress on the endoplasmic reticulum is an active contributor to the onset of Parkinson’s disease. Not only that, but the results show the ability to delay or prevent the progression of PD through ER targeted therapies. These drug therapies will help diminish the onset and progression of the diseases, adding years to patients’ lives.

Additional information on Parkinson’s disease

Parkinson’s disease is a disease of the central nervous system and 60,000 people in the United States are diagnosed with PD each year. The most obvious symptom of the disease is uncontrolled body movements when resting. Once the disease progresses further a patient can experience changes in their mood, dementia, problems with their senses and sleep difficulties.

Currently, treatment options for the disease are limited. Most treatments can increase dopamine levels in the brain, slowing the progression of the disease, but there is no treatment that will stop the neurons from dying altogether.