Epigenetic Mechanisms of Ischemic Stroke

Abstract

Stroke is one of the main causes of human death and disability. Occlusion of the cerebral vessels in minutes leads to oxygen and glucose depletion and the infarction of nervous tissue. However, neuroprotectors that can rescue neurons have not been found yet. This review describes the biochemical processes leading to cell death in the ischemic brain and the molecular factors that spread the damage to neighboring tissues and form the transition zone (penumbra). Even though ischemic damage generally suppresses biosynthetic processes, some proteins are expressed in the ischemic penumbra. Epigenetic processes are the mechanisms of the global regulation of transcription and protein synthesis as well as the functional state of cells. The review considers main epigenetic processes that regulate gene expression and protein synthesis: DNA methylation, methylation and acetylation of histones. The main attention is paid to epigenetic regulatory proteins: DNA methyltransferases, histone acetyltransferases, histone deacetylases and their isoforms. Their role in the brain responses to ischemic damage is discussed. The inhibition of some epigenetic proteins is one of the promising strategies for the treatment of ischemic stroke. The capabilities of some inhibitors of histone deacetylases and DNA methyltransferases as potential neuroprotectors in ischemic stroke are discussed.