Connecting the dots: Involvement of methyltransferase-like 3, N6-methyladenosine modification, and ferroptosis in the pathogenesis of intracerebral hemorrhage pathogenesis

Abstract

Intracerebral hemorrhage is a profoundly detrimental acute cerebrovascular condition with a low overall survival rate and a high post-onset disability rate. Secondary brain injury that ensues post-ICH is the primary contributor to fatality and disability. Hence, the mitigation of brain injury during intracerebral hemorrhage progression has emerged as a crucial aspect of clinical management. N6-methyladenosine is the most pervasive, abundant, and conserved internal co-transcriptional modification of eukaryotic ribonucleic acid and is predominantly expressed in the nervous system. Methyltransferase-like 3 is a key regulatory protein that is strongly associated with the development of the nervous system and numerous neurological diseases. Ferroptosis, a form of iron-associated cell death, is a typical manifestation of neuronal apoptosis in neurological diseases and plays an important role in secondary brain damage following intracerebral hemorrhage. Therefore, this review aimed to elucidate the connection between m6A modification (particularly methyltransferase-like 3) and ferroptosis in the context of intracerebral hemorrhage to provide new insights for future intracerebral hemorrhage management approaches.