Elucidating how Amyloid-Beta Changes Protein Expression in AD Brain
The search for the causes of transcriptional misregulation in disease is often aimed at finding individual transcription factors, but these proteins have important functions outside of pathology and are thus problematic as drug targets. Here, we are instead focusing on an interaction between two transcription factors in AD brain that leads to pathogenic changes in gene expression. Targeting this interaction, rather than the individual transcription factors might be a novel avenue for a disease-modifying therapy in AD. The successful completion of our research proposal will establish the concept that changes in protein expression in AD can be caused by the erroneous interaction between two transcription factors rather than by changes in their levels. We expect this principle to be apply to other diseases as well, esp. Parkinson's disease. The next step will be to investigate whether this mechanisms can be targeted therapeutically.