N6-methyladenosine modification in ischemic stroke: Functions, regulation, and therapeutic potential

Abstract

N6-methyladenosine (m6A) modification is the most frequently occurring internal modification in eukaryotic RNAs. By modulating various aspects of the RNA life cycle, it has been implicated in a wide range of pathological and physiological processes associated with human diseases. Ischemic stroke is a major cause of death and disability worldwide with few treatment options and a narrow therapeutic window, and accumulating evidence has indicated the involvement of m6A modifications in the development and progression of this type of stroke. In this review, which provides insights for the prevention and clinical treatment of stroke, we present an overview of the roles played by m6A modification in ischemic stroke from three main perspectives: (1) the association of m6A modification with established risk factors for stroke, including hypertension, diabetes mellitus, hyperlipidemia, obesity, and heart disease; (2) the roles of m6A modification regulators and their functional regulation in the pathophysiological injury mechanisms of stroke, namely oxidative stress, mitochondrial dysfunction, endothelial dysfunction, neuroinflammation, and cell death processes; and (3) the diagnostic and therapeutic potential of m6A regulators in the treatment of stroke.