Epigenomics dysregulation and therapeutics in neurodegeneration

Our results indicate a link between decreased cholesterol biosynthesis pathway and hyperacetylation in tauopathy, likely through the availability of their common primary substrate, acetyl-CoA. This work supports the use of molecules capable of activating the cholesterol/mevalonate pathway in the brain subjected to Tau-related neurodegenerative cognitive diseases (including Alzheimer's disease) and opens to the use of new epi-drugs. We are now studying these regulations in response to environmental cues, such as social and physical enrichment, which are emerging as powerful modifiers of disease progression in many neurodegenerative diseases, although their ability to alter the epigenomic landscape of the brain remains poorly described.