Alzheimer’s disease is characterized by the degeneration of neurons in the hippocampus and cortex, and the appearance of neuritic plaques and neurofibrillary tangles. Although the precise cause of Alzheimer’s disease remains unclear, and is in fact most likely from multiple etiologies. Over the past several years, a consensus has emerged that a cocktail of drugs influencing multiple mechanisms may be required to effectively treat Alzheimer’s disease, however, this has yet to be validated. Now, a study from researchers at the Salk Institute shows that boosting levels of a specific protein in the brain alleviates hallmark features of Alzheimer’s disease in a mouse model of the disorder. The team state that their findings suggest neuregulin-1 has broad therapeutic potential, and shows that it promotes metabolism of the brain plaques that are characteristic of Alzheimer’s disease. The opensource study is published in the journal Scientific Reports.
Previously studies show that treating cells with neuregulin-1 dampens levels of amyloid precursor protein, a molecule that generates amyloid beta, whose aggregates form plaques in the brains of Alzheimer’s patients. Other studies suggest that neuregulin-1 could protect neurons from damage caused by blockage of blood flow. The current study tests this hypothesis by raising the levels of one of two forms of neuregulin-1 in the hippocampus, an area of the brain responsible for learning and memory.
The current study utilises a mouse model of Alzheimer’s disease to show that both forms of the protein seemed to improve performance on a test of spatial memory in the models. Results show that 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. Data findings show that neuregulin-1 breaks up plaques by raising levels of an enzyme called neprilysin, shown to degrade amyloid-beta.
The group state that a neuregulin-1 treatment is not available on the market, though it is being explored in clinical trials as a potential treatment for chronic heart failure and Parkinson’s disease. They go on to add that one advantage of neuregulin-1 as a potential drug is that it can cross the blood-brain barrier, which means that it could be administered noninvasively even though the efficiency is not clear. They note that other research suggests too much of the protein impairs brain function.
The researchers state that they developed a small molecule which can raise levels of existing neuregulin-1, rather than administering it directly, and are testing it in cells. They explain that this alternative therapy could be a better way to prevent plaques from forming because small molecules more readily cross the blood-brain barrier.
The team surmise that their results suggest NRG1 provides beneficial effects in candidate neuropathologic substrates of Alzheimer’s disease and, therefore, is a potential target for the treatment of Alzheimer’s disease. For the future, the researchers are testing neuregulin-1’s affects across other models.