Histone Deacetylases in Stroke

Abstract

Stroke is the second leading cause of death and the leading cause of adult disability worldwide. Despite an impressive amount of neuroprotective agents that has been identified in experimental stroke, none of them proved efficient in clinical trials. There is a general consensus that an effective treatment requires the ability to interact with not one, but multiple pathophysiological cascades at different levels that induced by the insult – cocktail therapy. Luckily, recent progress in the field of epigenetics revealed that epigenetic modifications had influence on many known pathways involved in the complex course of ischemic disease development. The fact that epigenetic molecules, by altering transcriptional regulation, may simultaneously act on different levels of ischemic brain injury makes them promising candidates for clinical use. These modifications arise typically owing to deoxyribonucleic acid methylation and histone acetylation. The aim of this review is to give a comprehensive overview of current advances in stroke epigenetics, in particular, the physiological and pathological functions of the 11 classical histone deacetylases.

Stroke and Etiopathogenesis: What Is Known?

“…MiRNAs are described in cell proliferation and differentiation, apoptosis, fat metabolism and hematopoiesis [ 108 ]. LncRNAs are a regulator of vascular function, and their dysregulation contributes to cardiovascular disease [ 109 , 110 ]. Studies have revealed alterations in miRNA levels in arterial hypertension, dyslipidemia, atherosclerosis, and inflammation [ 111 , 112 , 113 , 114 ].…”

Epigenetic Regulations of Microglia/Macrophage Polarization in Ischemic Stroke

“…For example, HDAC inhibitors and DMNT inhibitors are not selective for brain regions and cell types ( Xu et al, 2020b ). Non-specific HDAC inhibitors may cause a variety of adverse reactions, including weight loss, dysgeusia, electrolyte changes, and arrhythmia ( Kao and Lin, 2019 ). So, it is more appropriate to choose epigenetic drugs that target specific epigenetic modifications rather than affect global modifications.…”

The protective role of endothelial GLUT1 in ischemic stroke

“…Aside from activation of transcription factors, histone modification is also common in stroke and also plays an important part in controlling GLUT1 gene transcription (Kao & Lin, 2019 ). Inhibition of histone deacetylase (HDAC) leads to significant GLUT1 acetylation and increases GLUT1 expression (Chen et al., 2015 ).…”