Epigenetics is essentially studying the mechanisms that turn genes on and off without actually altering the gene sequence. Neurodegeneration encompasses the loss of structure and function of neurons and eventual neuronal cell death. Currently the most common type of neurodegenerative disease is Alzheimer’s Disease (AD). Neuronal damage and associated gene misregulation have strong effects on cognitive function. To maintain proper cognitive functions epigenetic modifiers such as histone acetyltransferases (HATs) play a significant role. We have shown that disruption of Tip60 histone acetlytransferase (HAT)/histone deacetylase 2 (HDAC2) homeostasis occurs early in the brain of an AD drosophila model and triggers epigenetic repression of neuroplasticity genes. We have demonstrated that increasing Tip60 HAT restores the HAT/HDAC2 balance and reverses neuroepigenetic alterations and reinstates brain morphology and cognition. We have suggested that Tip60 HAT/HDAC2-mediated epigenetic gene disruption is a critical initial step in AD that is reversed by restoring Tip60 activity in the brain.
