We know that regular exercise is good for us, and now researchers have learned more about why vigorous activity can slow the progression of Parkinson’s disease. Until now, the underlying causes have been a mystery. Researchers used a mouse model of age-related Parkinson’s disease to show that the neuronal protein alpha-synuclein stopped accumulating when the mice used a running wheel.
The work, reported in PLOS One, was led by Wenbo Zhou, Ph.D., research associate professor of medicine and Curt Freed, M.D., professor of medicine and division head of the Division of Clinical Pharmacology and Toxicology at the CU School of Medicine.
It had been thought that the brain cell death observed in Parkinson’s is related to the clumping of alpha-synuclein proteins. A mouse model of the disease starts to show signs of Parkinson’s in mid-life, and at twelve months old, the researchers gave the mice running wheels.
"After three months, the running animals showed much better movement and cognitive function compared to control transgenic animals which had locked running wheels,” explained Zhou.
The researchers found that there was an increase in the expression of a gene called DJ1 in the brain and muscle tissue. The gene has a protective effect, and it has been established that in rare cases of humans who carry a mutation in the DJ-1 gene, they get Parkinson’s disease at a relatively young age. Mice that lacked the DJ-1 gene were tested and found to have severe declines in their ability to run. That suggested to the investigators that DJ-1 is essential for normal movement.
"Our results indicate that exercise may slow the progression of Parkinson's disease by turning on the protective gene DJ-1 and thereby preventing abnormal protein accumulation in [the] brain," Freed said. He noted that these animal findings have genuine implications for human patients.
"Our experiments show that exercise can get to the heart of the problem in Parkinson's disease," Freed said. "People with Parkinson's who exercise are likely able to keep their brain cells from dying."
Brain cells that synthesize a vital chemical called dopamine start to die off in Parkinson’s disease. Dopamine is required for normal voluntary movement, so as the levels decrease, movement becomes much more challenging for patients. They often take a drug called L-DOPA to try to relieve the symptoms. The drug is converted in dopamine in the brain, enabling movement.
Freed and his colleague Robert Breeze, M.D., were the first to perform a transplant of human fetal dopamine cells into a Parkinson's patient in the United States, in 1988. Now, his lab is working to derive dopamine neurons from human embryonic stem cells. Once that goal is realized, it should then be possible to generate an unlimited amount of dopamine cells for transplant.
Learn more about exercise and Parkinson's disease from the video.
Sources: AAAS/Eurekalert! Via University of Colorado, PLOS One