Targeting Epigenetics in Ischemic Stroke: From Mechanisms to Therapeutics

Ischemic stroke is the main cause of death and disability in human diseases worldwide. Due to the complexity of its pathophysiological mechanism, the treatment effect is not ideal. Epigenetics refers to the mechanisms of affecting gene function and expression by chemical modification or chromatin structure without changing the DNA sequence. The epigenetic network is mainly composed of various epigenetic modifying enzymes (such as DNA methyltransferase/demethylase, DNMT/tet, histone methyltransferase/demethylase, HMT/hdm, histone acetyltransferase/deacetylase hat/hdac) and non-coding RNAs with different functions. Epigenetic enzymes or non-coding RNAs can participate in the core pathophysiological processes after ischemic stroke, such as neuroinflammation, oxidative stress, and cell apoptosis, by regulating the activation or silencing of key gene transcription. Due to the regulatory role of epigenetic modifying enzymes and non-coding RNAs after ischemic stroke, targeted intervention of these epigenetic modifying enzymes and non-coding RNAs has been confirmed to improve the pathological process and neurological outcome after ischemia. Therefore, they are regarded as a series of therapeutic targets with great research and development potential. This study systematically reviewed the role and mechanism of DNA methylation, histone modification, and non-coding RNA in the pathological development of ischemic stroke, and discussed the research progress of related therapeutic drugs targeting these epigenetic modifying enzymes, in order to provide a theoretical basis and ideas for the development of new clinical diagnosis and treatment strategies for ischemic stroke.