Previous research suggests that a protein called Fyn becomes overactive in the brains of people with Alzheimer’s disease. This overactivity has been linked to damage to nerve cells and their connections. Drugs that could dampen down Fyn overactivity are being explored as potential Alzheimer’s treatments. Researchers led by Dr Mariana Vargas-Caballero are investigating the effect these drugs will have on the brain and aim to inform efforts to improve their effectiveness and safety.
As Alzheimer’s disease develops, proteins that normally help cells in the brain to stay healthy start to act differently and cause damage. The Fyn protein is normally involved in supporting communication between nerve cells, but overactive Fyn appears to contribute to harmful disease processes, potentially by interacting with the hallmark Alzheimer’s protein, tau. Using drugs to limit Fyn activity is a promising approach for slowing the progression of Alzheimer’s, but we need to know if this could have unwanted or harmful side effects. This project is essential to understand whether drugs that block Fyn protein have positive or negative long-term effects to the brain, and the results from this research will help the future development of potential Fyn-based therapies.
The team will study the effects of blocking the activity of Fyn in healthy mice and mice with features of Alzheimer’s disease. They will carefully study changes to nerve cells, assessing their ability to maintain or strengthen their connections – important processes for healthy brain function. The team will also zero in on how Fyn and tau proteins interact and aim to reveal more about Fyn’s role in Alzheimer’s. By examining the biological effects of Fyn suppression, the study will either provide further confidence to the use of drugs that target Fyn activity in Alzheimer’s disease, or highlight side effects so that current drugs can be further improved.
Dr Mariana Vargas-Caballero
University of Southampton
1 September 2018 - 31 August 2021
Full project name
Ups and downs of NMDA receptor phosphorylation by Fyn kinase: relevance for synaptic function in AD