Histone and non-histone (de)acetylation impact on the blood-brain barrier

The blood-brain barrier (BBB) ensures the homeostasis of the central nervous system by regulating the composition of the brain interstitial fluid, required for proper brain function. Nonetheless, its properties are dynamic and susceptible to the influence of environmental factors acting through epigenetic mechanisms, among which are post-translational histone modifications. The activity of histone acetylases (HATs) and histone deacetylases (HDACs) on histone and non-histone substrates can alter gene transcription in brain endothelial cells, pericytes, astrocytes and microglia, leading to protective or detrimental effects on BBB integrity and function. These effects may range from the stabilization of intercellular junction proteins in brain endothelial cells to the modulation of neuroinflammation, with consequences on cognitive processes of memory and learning. Ultimately, the positive or negative outcome of HAT/HDAC activity is often context-dependent and varies across different pathologies, according to which corepressors or coactivators are recruited in intracellular signaling cascades, and their subsequent influence on gene expression. HATs/HDACs modulate the structural integrity and function of the BBB. Further studies in physiologically relevant BBB models are required, in order to provide greater mechanistic insight and overcome translational difficulties.