Brain HealthHow the REST Transcription Factor Guards Aging Neurons Against Degeneration
REST (RE1-silencing transcription factor) is a master epigenetic regulator that controls which genes are switched on or off in neurons. Originally known for silencing neuronal genes in non-neuronal cells, REST turns out to play a much broader role — shaping how neurons develop, mature, and survive as the brain ages. In aging neurons, nuclear REST helps regulate stress-response genes that keep cells resilient. When REST activity is disrupted or mislocalized, the consequences can be severe: altered REST function has been linked to Alzheimer's and Huntington's disease. REST also interacts with microRNAs like miR-9 and miR-124, metabolic signals involving the NAD+/NADH ratio, and potentially environmental factors such as exercise. This review synthesizes the current evidence and maps out important knowledge gaps that future research must address.
