Raising brain protein alleviates symptoms of Alzheimer's disease in mouse model

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The protein at the center of the study is neuregulin-1 - a genetic target for Parkinson's disease schizophrenia and Lou Gehrig's disease or motor neurone disease that has affected Stephen Hawking.

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.

"Neuregulin-1 has broad therapeutic potential, but mechanistically, we are still learning about how it works", Lee said. In order to test this, researchers from Salk Institute used a mouse model of Alzheimer's disease.

In relation to Alzheimer's, scientists have previously demonstrated that Neuregulin-1 can lower the levels of amyloid precursor proteins - molecules responsible for generating the risky amyloid beta plaques in Alzheimer's patients' brains - on a single cell basis. Other studies suggest that neuregulin-1 could protect neurons from damage caused when the flow of blood is blocked. "We've shown that it promotes metabolism of the brain plaques that are characteristic of Alzheimer's disease". For the new study, the team raised the levels of the protein in the hippocampus of the brains of laboratory mice with the disease, studying them to see whether similar positive effects were observed. Both forms of the protein seemed to improve performance on a test of spatial memory in the models. Compared to mice not treated, levels of amyloid beta and plaques were lower in rodents receiving treatment.

According to the study findings, neuregulin-1 disbands plaques by upping the levels of neprilysin enzyme, which impairs amyloid-beta.

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. On the other hand, other research suggests too much of the protein impairs brain function.

Looking forward, the team has developed a molecule that's able to raise levels of existing neuregulin-1 in a patient's system, rather than administering it directly. This alternative therapy could be a better way to prevent plaques from forming because small molecules more readily cross the blood brain barrier. An adjustment in the neuregulin-1 gene-a single change in one letter of the DNA code for the protein-has been found in families with schizophrenia and linked to late-onset Alzheimer's disease with psychosis.

An important caveat is that the new research was conducted in a single type of mouse model of Alzheimer's. "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.