Researchers have identified a human enzyme that might protect brain cells.
The University of Kentucky team found that the enzyme lessens the damage caused by strokes and Alzheimer’s disease– knowledge that might lead to treatments to slow the devastating disorders.
The enzyme–with the tongue-twisting name manganese superoxide dismutase, or MnSOD–prevents buildups of free radicals, the cell-damaging molecules released by strokes or by the effects of Alzheimer’s, said neurobiologist Mark Mattson.
“Our data suggest that if one can artificially increase levels of this enzyme, cells may become more resistant to degeneration,” Mattson said. “We are working now to find potential therapeutic agents that either increase levels of the enzyme or mimic its activity.”
Mattson and his colleagues may have found one agent–uric acid–that acts like MnSOD.
When they gave uric acid to mice and rats, then induced strokes in the animals about an hour later, they suffered significantly less brain damage than mice and rats that were given strokes without uric acid. If future experiments go well, it might be possible to test uric acid as a stroke treatment within five years, researchers said.
The report, involving biologists, biochemists, neurobiologists and toxicologists from the university and the Sanders-Brown Center on Aging, was reported this month in the Journal of Neuroscience.
The study fits in with other research identifying superoxide dismutase for its ability to forestall cell death, said Dr. David Comings, director of the Department of Medical Genetics at the City of Hope National Medical Center in Duarte, Calif.
Also, if uric acid can act like the enzyme, that finding enhances the university’s study, Comings said, because it “takes it out of academia to one which may have treatment application.”
Alzheimer’s and strokes are two of the nation’s biggest health problems. There is no cure for Alzheimer’s, a fatal, degenerative brain disease that mostly strikes older people.
Strokes, which kill or disable more than 500,000 people each year, are the nation’s third-leading cause of death. Stroke treatments have improved, but doctors still have relatively few weapons against the disorder. Strokes occur when blood vessels running to the brain clog up or burst.
The cause of Alzheimer’s is unknown, but scientists think the diseases and some other neurological disorders kill brain cells by causing buildups of free radicals, toxic oxygen molecules that destroy healthy cells.
As a result, there has been an increasing interest in anti-oxidants such as vitamin E and vitamin C that combat free radicals.
The university’s research is the first to show that a specific enzyme, MnSOD, also plays a key role in protecting cells by blocking production of a free radical called superoxide.
According to Mattson, MnSOD occurs naturally in cells, but he speculates the damage caused by strokes and Alzheimer’s is so great that it overwhelms the natural levels of the enzyme so it can’t prevent damage.
To test the theory, the research team cultured mice and human brain cells, genetically altering them to produce high levels of MnSOD, then subjected the cells to stresses like those caused by strokes or Alzheimer’s.
In another experiment, mice were genetically altered to produce high levels of MnSOD and then subjected to strokes.
In each case, the enzyme appeared to protect the cells.
Mattson also displayed dramatic slides of microscopic brain samples from rats in which strokes were induced. In rats that had been given uric acid just before the strokes, brain damage was noticeably less than in rats which were not given uric acid, a naturally occurring substance.
Biochemist Mark Kindy said that in some cases rats protected by uric acid could still move well after the strokes while rats not given uric acid had little mobility.
The next question, Mattson and Kindy said, is whether uric acid can protect brain cells after a stroke. If it does, they said, the substance might be developed into a stroke treatment.
With support from medical centers, human clinical trials of uric acid could be possible within five years, Mattson said.
Even if uric acid could slow or ease the severity of Alzheimer’s or stroke symptoms, it wouldn’t constitute a cure, Mattson said. He added that their findings strengthen the case that anti-oxidants might be a hedge against Alzheimer’s.
“Our work will have no short-term implications for Alzheimer’s patients,” he said. “I would say to those patients that, with our current state of knowledge, they should be taking anti-oxidants, vitamin E, vitamin C.”
