A study by Massachusetts General Hospital researchers adds further support to the possibility that increasing levels of the antioxidant urate may protect against Parkinson's disease. In their report published in PNAS Early Edition, the investigators report that mice with a genetic mutation increasing urate levels were protected against the kind of neurodegeneration that underlies Parkinson's disease, while the damage was worse in animals with abnormally low urate.
"These results strengthen the rationale for investigating whether elevating urate in people with Parkinson's can slow progression of the disease," says Xiqun Chen, MD, PhD, of the MassGeneral Institute for Neurodegenerative Diseases (MGH-MIND) and lead author of the PNAS report. "Our study is the first demonstration in an animal model that genetic elevation of urate can protect dopamine neurons from degeneration and that lowering urate can conversely exacerbate neurodegeneration."
Characterized by tremors, rigidity, difficulty walking and other symptoms, Parkinson's disease is caused by destruction of brain cells that produce the neurotransmitter dopamine. Healthy people whose urate levels are at the high end of the normal range have been found to be at reduced risk of developing Parkinson's disease. Studies led by Michael Schwarzschild, MD, PhD, director of Molecular Neurobiology Laboratory at MGH-MIND, showed that, among Parkinson's patients, symptoms appear to progress more slowly in those with higher urate levels. These observations led Schwarzschild and his colleagues to develop the SURE-PD (Safety of URate Elevation in Parkinson's Disease) clinical trial, conducted at sites across the country through the support of the Michael J. Fox Foundation. Expected in early 2013, the results of SURE-PD will determine whether a medication that elevates urate levels should be tested further for its ability to slow the progression of disability in Parkinson's disease.
The current study by Schwarzschild's team was designed to improve understanding of how urate protects against neurodegeneration. As in most animals, mice normally have very low levels of the antioxidant because it is broken down by the enzyme urate oxidase or uricase. The higher urate levels seen in humans and great apes were caused by inactivation of the uricase gene during primate evolution. The MGH-MIND team used two strains of genetically altered mice. In one, the gene for uricase is knocked out as it is in humans, increasing urate levels in the blood and brain; in the other strain, the gene is overexpressed, reducing urate levels even lower than usual for mice. Animals from both strains were used in a standard Parkinson's modeling procedure in which a neurotoxin is injected into the dopamine-producing brain cells on one side of the brain.
As expected, the brains of animals with genetically elevated urate levels showed significantly less damage from the neurotoxin injection than did the brains of genetically normal mice. The damage was increased even more in the mice with genetically reduced urate levels, which also exhibited reduced dopamine production and worsened movement abnormalities. The researchers confirmed that genetically altering uricase expression did not affect levels of other molecules in the metabolic pathway that includes urate, supporting attribution of the protective role to urate alone.
"The biology of urate in the brain is largely unexplored," says Schwarzschild, an associate professor of Neurology at Harvard Medical School. "Understanding both urate's mechanisms of protection and the way its levels are regulated in the body will help us determine how to better harness its protective effects, if they are substantiated. We now are searching for the mediators of urate's neuroprotection and beginning to explore how it is generated and transported in different brain cells."
Massachusetts General Hospital: http://www.mgh.harvard.edu
This press release was posted to serve as a topic for discussion. Please comment below. We try our best to only post press releases that are associated with peer reviewed scientific literature. Critical discussions of the research are appreciated. If you need help finding a link to the original article, please contact us on twitter or via e-mail.
Wild birds identify “good” seeds without first opening the shells by weighing them and by listening to the sound produced when clicking their beaks on the shell, according to a recent study
139 new species were identified in South East Asian region in 2014, including four moths named after Thai princesses and a new mammal
A genetically engineered version of a virus that normally causes cold sores shows real promise for treating skin cancer, say researchers.
An experimental Parkinson's treatment abandoned in the 1990s has been revived – and could restore a person's control of their movement within five years
The White House said on Tuesday the ethical issues associated with gene-editing on the human genome need further study by the scientific community and should not be pursued until issues are resolved.
The ancient water supply system was discovered by construction workers digging a new sewer
Faux eggs made with 3-D printers are better than sculpted versions, researchers say, because it's easier to systematically vary their size, weight and other features. Next goal: 3-D fragile shells.
The problem has gotten so bad that some doctors are pondering a "post-antibiotic world." The World Health Organization says countries need to boost surveillance for resistance and develop new drugs.
Anglo-Saxon headgear reconstructed from more than 1,500 pieces as £400,000 grant is announced to fund further work on the treasure
The smallest and rarest marine dolphin in the world could be extinct within 15 years if protection is not stepped up, according to research.