Deliniating Pathways Downstream of Keap 1-Nrf2 as Targets for Neuronal Protection in AD

Amyloid (Aβ) deposits in the brain are thought to initiate nerve cell damage in Alzheimer’s Disease (AD). Nrf2 is a protein responsible for the protection of these cells and drugs stimulating its activity are successful in reducing damage in mouse AD models. Toxicity to humans however has led research to Keap1 blockers, a protein that prevents Nrf2 function. There has been success with these blockers in fruit fly and mouse nerve cells, but we need to understand why these drugs work and their relevance to human AD. Using advanced molecular biology techniques, my project aims to profile the cascade of molecules responsible for protection of human nerve cells against Aβ damage following treatment with the Keap1-Nrf2 blocker, 18e. AD affects millions of people worldwide and a treatment is urgently required. This study will provide clues towards new targets for safer Nrf2-activating drugs to slow-down nerve cell damage in AD.