Researchers at the Salk Institute have alleviated characteristics of Alzheimer's disease by boosting a protein in the brains of mice bred to develop the condition, according to a study published in Scientific Reports.
The protein, called neuregulin-1, has many forms and functions across the brain and is already a potential target for brain disorders such as Parkinson's disease, amyotrophic lateral sclerosis and schizophrenia.
Although researchers are still figuring out how the protein works, "We've shown that it promotes metabolism of the brain plaques that are characteristic of Alzheimer's disease," says professor Kuo-Fen Lee.
Previous research found that treating cells with neuregulin-1 lowers levels of amyloid precursor protein, a molecule that generates amyloid beta. Amyloid beta clumps and forms plaques in the brains of Alzheimer's patients. Other studies suggest that neuregulin-1 could protect neurons from damage caused when the flow of blood is blocked.
In the new study, Lee and his team tested raised the levels one of two forms of neuregulin-1 in the hippocampus, an area of the brain responsible for learning and memory. Both forms of the protein seemed to improve performance on a test of spatial memory in the mice.
In addition, the levels of cellular markers of disease, including the levels of amyloid beta and plaques, were noticeably lower in mice with more neuregulin-1 compared to controls.
The study suggests that neuregulin-1 breaks up plaques by raising levels of an enzyme called neprilysin, that has been shown to degrade amyloid-beta. The group is also exploring other possible mechanisms, such as whether the protein improves signaling between neurons, which is impaired in Alzheimer's.
Neuregulin-1 isn't available to the public, but it is also being explored as a possible treatment for chronic heart failure and Parkinson's disease. Since the protein can cross the blood-brain barrier, it could be administered noninvasively.
Lee and his team have created a method of raising existing levels of neuregulin-1, which could help prevent plaque from forming.
"There's much more work ahead before neuregulin-1 could become a treatment, but we are excited about its potential, possibly in combination with other therapeutics for Alzheimer's disease," Lee says.
Scientists are testing another protein — IL-33 — for treating Alzheimer's. "IL-33 is a protein produced by various cell types in the body and is particularly abundant in the central nervous system — brain and spinal cord," said Professor Eddy Liew of the University of Glasgow. "We carried out experiments in a strain of mice (APP/PS1) which develop progressive AD-like disease with aging.
"We found that injection of IL-33 into aged APP/PS1 mice rapidly improved their memory and cognitive function to that of the age-matched normal mice within a week."
Researchers believe IL-33 also works by producing neprilysin, which destroy plaques by digesting them, thus reducing their number and size.
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