Researchers at the the Salk Institute, in California, have shown, in a mouse study, that increasing the levels of a specific protein in the brain leads to improvement of memory deficits associated with Alzheimer’s disease.
The new study, titled “Neuregulin 1 Improves Cognitive Deficits And Neuropathology In An Alzheimer’s Disease Model,” was published in the journal Scientific Reports.
The protein, neuregulin-1, has several forms and functions in the brain, most of which are known to play an important role in many disorders, such as Parkinson’s disease, autism, amyotrophic lateral sclerosis and schizophrenia. Other studies have suggested that neuregulin-1 may exert a protective effect by inducing a decrease in the levels of amyloid precursor protein, a molecule that generates amyloid beta, which is the primary component of the plaques that accumulate in the brain of Alzheimer’s patients, or by protecting neurons against the damage caused by blockage of blood flow.
“Neuregulin-1 has broad therapeutic potential, but mechanistically, we are still learning about how it works,” Kuo-Fen Lee, the lead author of the study, said in a news release. “We’ve shown that it promotes metabolism of the brain plaques that are characteristic of Alzheimer’s disease.”
In this study, the team tested, in mice, the effect of increased levels of two forms of neuregulin-1, one at a time in the hippocampus, the brain region responsible for memory and learning. Researchers observed that both forms of neuregulin-1 were able to improve animal performance on a test of spatial memory, and that markers of Alzheimer’s, such as amyloid beta and plaques, had lower levels compared to the control animals.
The team believes that neuregulin-1 induced the expression of another protein, neprisylin, which is able to degrade amyloid beta and thus prevent the formation of plaques. However, the protein also may have other roles that contribute to its beneficial effect, such as improving signaling between neurons, which is altered in Alzheimer’s disease.
A neuregulin-1 treatment is currently undergoing trials as a possible therapy for Parkinson’s disease and chronic heart failure. Since this is a protein that can enter the blood brain barrier (a barrier that selects what enters the brain and what does not), a potential treatment with neuregulin-1 would not require an invasive procedure.
Researchers are currently trying to reproduce their results in other models while studying other relevant aspects that may support a possible treatment with neuregulin-1 for Alzheimer’s disease. For instance, as other studies suggested that too much neuregulin-1 can have an undesired effect on the brain, the team is testing a small molecule that can increase the levels of existing neuregulin-1, instead of administering more protein. They also are investigating the possible link between schizophrenia and psychosis in late-onset Alzheimer’s, as neuregulin-1 has been associated with both disorders.
“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 said.