June 28, 2016
A key enzyme, c-Abl, provides clues about Parkinson’s disease to researchers who say blocking the enzyme prevented the disease in specially bred mice.
Up to 1 million Americans have Parkinson’s disease, with about 60,000 newly diagnosed cases in the U.S. each year, according to the Parkinson’s Disease Foundation. The progressive disease affects movement and symptoms often include tremors and stiff movements.
A team, led by Ted Dawson, M.D., Ph.D., a professor of neurology and director of the Institute for Cell Engineering at the Johns Hopkins University School of Medicine, investigated the activity of c-Abl after earlier indications suggested there was a link to Parkinson’s disease, a connection which the new research confirms, the scientist said. A drug used to treat leukemia that inhibits c-Abl is already approved by the Food and Drug Administration. The drug, nilotinib, could provide a jumping off point to develop other treatments for Parkinson’s.
It was unclear in earlier animal studies if drugs blocking c-Abl were also blocking similar proteins that were causing benefits such as slowing disease progression or preventing symptoms.
In the new study, researchers knocked out the gene for c-Abl in genetically engineered Parkinson’s mouse models and when they did so, the mice saw a reduction in their symptoms. On the other hand, when scientists amped up the amount of the enzyme, mice experienced worse symptoms and disease progression sped up. Healthy mice also ended up developing Parkinson’s disease when production of c-Abl was increased.
The researchers believe the cause of this has something to do with the enzyme’s interaction with the protein α-synuclein. Clumping of α-synuclein in the brain is a known characteristic of Parkinson’s. According to Dawson, the researchers discovered that the enzyme adds a molecule on α-synuclein and increasing the amount of c-Abl caused more clumping along with increased symptoms.
“We plan to look into whether α-synuclein with a phosphate group on the spot c-Abl targets could serve as a measure of Parkinson’s disease severity,” Dawson said in a prepared statement. No biochemical marker exists as of now and this could help Parkinson’s disease research more broadly, according to the researchers. While certain genetic variants and environmental factors such as exposure to toxins or injury, may be linked to Parkinson’s, the cause is still unknown.
The findings were published June 27 in The Journal of Clinical Investigation.
http://www.biosciencetechnology.com/news/2016/06/parkinsons-symptoms-halted-mice-after-enzyme-blocked
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