A newly developed nanomaterial that mimics the behavior of proteins could be an effective tool for treating Alzheimer’s and other neurodegenerative diseases. The nanomaterial alters the interaction between two key proteins in brain cells — with a potentially powerful therapeutic effect.

The innovative findings, recently published in the journal Advanced Materials, were made possible thanks to a collaboration between University of Wisconsin–Madison scientists and nanomaterial engineers at Northwestern University.

The work centers around altering the interaction between two proteins that are believed to be involved in setting the stage for diseases like Alzheimer’s, Parkinson’s and amyotrophic lateral sclerosis, or ALS.

The first protein is called Nrf2, a specific type of protein called a transcription factor that turns genes on and off within cells.

One of Nrf2’s important functions is its antioxidant effect. While different neurodegenerative diseases result from separate disease processes, a commonality among them is the toxic effect of oxidative stress on neurons and other nerve cells. Nrf2 combats this toxic stress in brain cells, helping to stave off disease.

Jeffrey Johnson, a professor in the UW–Madison School of Pharmacy, has been studying Nrf2 as a promising target for treating neurodegenerative diseases for decades alongside his wife Delinda Johnson, a senior scientist at the pharmacy school. In 2022, the Johnsons and another group of collaborators found that increasing Nrf2 activity in a specific cell type in the brain, the astrocyte, helped protect neurons in mouse models of Alzheimer’s disease, leading to significantly less memory loss.

While this previous research suggested that increasing Nrf2’s activity could form the basis of an Alzheimer’s treatment, scientists have found it challenging to effectively target the protein within the brain.

“It’s hard to get drugs into the brain, but it’s also been very hard to find drugs that activate Nrf2 without a lot of off-target effects,” says Jeffrey Johnson.

Enter the new nanomaterial. Known as a protein-like polymer, or PLP, the synthetic material is designed to bind to proteins as if it were itself a protein. This nano-scale imitator is a product of a team led by Nathan Gianneschi, a professor of chemistry at Northwestern and faculty member at the university’s International Institute for Nanotechnology.