New approach limits Alzheimer’s damage in mice and flies

03 March 2017

PLOS Genetics:  Direct Keap1-Nrf2 disruption as a potential therapeutic target for Alzheimer’s disease

Researchers from UCL (University College London) have found that blocking the action of a protein called Keap1 could help to protect nerve cells in the brain from damage by proteins that build up in Alzheimer’s disease. The research, which investigated the activity of proteins in fruit flies and mice, is published today (2 March) in the journal PLOS Genetics.

Alzheimer’s is a complex disease associated with a number of changes in the brain. A central change is the build-up of a protein called amyloid, which scientists believe kick-starts other downstream changes that damage nerve cells. A protein called Nrf2 can help to protect cells from damaging processes but levels of this protein are lower in the brains of people with Alzheimer’s than others.

Methods of boosting the levels of Nrf2 in Alzheimer’s have been explored by previous research, but many of these approaches have had unintended consequences that were harmful to cells. In this study the researchers targeted a protein called Keap1 that directly interacts with Nrf2 and blocks the action of the protective protein.

Using a chemical compound that prevents the Keap1 protein from interacting with Nrf2, the researchers showed that they were able to limit the harmful effects of amyloid in fruit flies and to nerve cells in mice.

Dr Laura Phipps of Alzheimer’s Research UK, said:

“There are over 500,000 people living with Alzheimer’s in the UK but there are currently no treatments that can slow the disease or protect nerve cells in the brain from damage. This study suggests a possible new way to enhance the brain’s ability to protect itself from harmful Alzheimer’s processes. While there have been several high-profile failures of drugs targeting the amyloid protein directly, this approach aims to block this toxic chain of events further upstream. Alzheimer’s is a complex disease and we have the best chance of success if researchers tackle it from as many different angles as possible.

“Alzheimer’s Research UK is pleased to have funded this interesting work, which will help to inform future research into the potential benefits of harnessing this protective mechanism. Discoveries in mice and fruit flies are an important step in the research process but for these findings to have an impact on the lives of people with Alzheimer’s in future, investment in research must continue.”