HARTFORD, Conn. -- Yale researchers say inhibiting a protein in the brain may be key to reversing the effects of Alzheimer's disease.
In a study published Monday in Proceedings of the National Academy of Sciences, the team of researchers points to high levels of a protein known as Striatal-Enriched tyrosine Phosphatase, or STEP, as a major factor in Alzheimer's.
Based on previous studies that have shown an elevated activity of STEP in humans with Alzheimer's, the Yale researchers conducted tests on two sets of mice. Both were genetically engineered to have Alzheimers, but one set was also engineered to have its STEP protein levels reduced. They found that the mice with reduced STEP were eventually able to complete mazes in the same time as mice without Alzheimer's.
"The importance of that study is that it suggested that reducing STEP levels genetically reduces" the effects of Alzheimer's, said Paul Lombroso, senior author of the study.
What the excess of STEP does, he said, is damage certain neurons. Specifically, the protein removes glutamate receptors on the neurons' surface, which are crucial to forming long-term memories.
"This suggests that a too-high level of STEP, by removing glutamate receptors, is stripping away the ability to memorize and learn," said Lombroso, professor in the Yale Child Study Center and in the Departments of Neurobiology and Psychiatry at Yale School of Medicine.
Other studies have indicated the STEP plays a similar role in schizophrenia and fragile x, a form of mental retardation.
Lombroso said the mice with reduced levels of STEP showed a complete reversal of the effects of Alzheimer's by six months. More research, he said, is required to see if any of the symptoms of Alzheimer's would return with more time.
Lombroso said he hopes additional research will lead to the development of a drug that could inhibit the STEP protein and treat Alzheimer's in humans.
Asked whether excessive STEP levels play a factor in the routine dulling of the mind that often comes with aging, Lombroso said that had not been ruled out, but that no research had been conducted.
"We're looking at whether or not there's a disruption in STEP function in these older mice and rats, but there's no data," he said.
Chris Van Dyck, director of Yale's Alzheimer's Disease Research Unit, called the paper "exciting research."
"We know that with Alzheimer's disease, synaptic function is key to cognitive deficit," said Van Dyck, who was not a part of the study. "This is an important paper that attempts to explain that." In the process, he added, a possible treatment could realistically arise from it.
He said, though, that a good deal more research is needed to know what these results mean "because mice are not people and these Alzheimer's mouse models are limited."
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