While studying the effects of exendin-4 on the pancreas, Dr. Egan and her colleagues found that it also seemed to have beneficial effects on the brain. Specifically, GLP-1 stimulates the growth of neurites (developing neurons) in cell culture, and both GLP-1 and exendin-4 protect mature neurons against cell death. In fact, research increasingly suggests that there may be a link between some neurodegenerative disorders and metabolic dysfunction. The hope is that drugs, such as exendin-4, that enhance metabolic function may also be useful in the treatment of neurologic disease.

Building on these findings, Dr. Egan and others in the NIA Intramural Research Program have tested exendin-4 in cellular and mouse models of several neurodegenerative diseases. The results are promising. For example, using a mouse model of Huntington’s disease, they found that exendin-4 reduces the accumulation of the mutant huntingtin protein, which is implicated in the disease’s onset and progression. The treatment also improved motor function and extended the survival time of the Huntington’s disease mice.

In other studies, investigators found that exendin-4 significantly reduced levels of amyloid beta protein (a hallmark of Alzheimer’s disease) and its precursor molecule in mice models of the disorder. It also proved beneficial in cellular and animal models of another neurodegenerative disorder, amyotrophic lateral sclerosis (ALS), or Lou Gehrig’s disease.

via National Institute on Aging | The Leader in Aging Research.