Jeffrey and Delinda Johnson work in their lab on the UW–Madison campus. Credit: Sally Griffith/Oh/UW–Madison
Key points:
- The transcription factor Nrf2 plays a key role in combating toxic stress in the brain to stave off neurodegenerative diseases.
- Scientists developed a synthetic nanomaterial known as protein-like polymer (PLP) that alters the interaction between Nrf2 and Keap1 proteins.
- The research team showed that PLP effectively bound to Keap1 to allow Nrf2 to accumulate and amp up its antioxidative function.
Scientists have developed a potential treatment option for Alzheimer’s and other neurodegenerative diseases using a nanomaterial that mimics the behavior of proteins. This exciting discovery, published in Advanced Materials, alters the interaction between proteins in brain cells in a way that may have therapeutic effects.
Different neurodegenerative diseases result from separate disease processes, but all share the toxic effect of oxidative stress on neurons and other nerve cells. The protein Nrf2—a transcription factor that turns genes on and off within cells—plays a key role in combating toxic stress in the brain to stave off disease. To date, researchers have found it difficult to effectively target Nrf2 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,” explained study author Jeffrey Johnson, professor at University of Wisconsin-Madison.
Now, researchers have developed a synthetic nanomaterial known as a protein-like polymer (PLP) that can bind to proteins as if it were a protein itself. They used a PLP that altered the interaction between Nrf2 and the Keap1 protein, which controls when Nrf2 responds to and combats oxidative stress.
The research team found that PLP was very effective at binding to Keap1 and freeing up Nrf2 to accumulate in cells’ nuclei and increase its antioxidant abilities. The PLP did not have off-target effects that would impact other strategies aimed at better activating Nrf2.
In the current study, researchers assayed PLP in cells in culture. As a next step, the team will investigate PLP in mouse models of neurodegenerative diseases.