Regulation of N6-methyladenosine (m6A) RNA methylation in microglia-mediated inflammation and ischemic stroke

Abstract

N6-methyladenosine (m6A) is the most abundant post-transcription modification, widely occurring in eukaryotic mRNA and non-coding RNA. m6A modification is highly enriched in the mammalian brain and is associated with neurological diseases like Alzheimer’s disease (AD) and Parkinson’s disease (PD). Ischemic stroke (IS) was discovered to alter the cerebral m6A epi-transcriptome, which might have functional implications in post-stroke pathophysiology. Moreover, it is observed that m6A modification could regulate microglia’s pro-inflammatory and anti-inflammatory responses. Given the critical regulatory role of microglia in the inflammatory processes in the central nervous system (CNS), we speculate that m6A modification could modulate the post-stroke microglial inflammatory responses. This review summarizes the vital regulatory roles of m6A modification in microglia-mediated inflammation and IS. Stroke is associated with a high recurrence rate, understanding the relationship between m6A modification and stroke may help stroke rehabilitation and develop novel therapies in the future.

The Activation of M1 Macrophages is Associated with the JNK-m6A-p38 Axis in Chronic Obstructive Pulmonary Disease

“… 24–27 The expression of p38, ERK, and JNK is influenced by a variety of factors, with m6A RNA methylation being one of the most common post-transcriptional modifications documented in a variety of inflammatory diseases. 28 Consistent with our findings, m6A regulators may be involved in the inflammatory response induced by M1 macrophage hyperactivation by regulating the MAPK signaling pathway, thereby participating in the development of COPD. 10 , 29 , 30 …”

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

“…Stroke-related neuroinflammation is a unique therapeutic target that contributes to the inhibition of secondary cell death and improves patient outcomes [ 135 ]. Microglia and infiltrated macrophages have been established to play important roles in the inflammatory processes postischemic stroke [ 136 ], which can be modulated by m 6 A regulators [ 137 ].…”

m6A methylation: Critical roles in aging and neurological diseases

“…Glial cells are the most abundant cells and induce several changes in pathological conditions such as inflammation, demyelination and disruption of BBB ( You et al, 2022 ). RNA m6A modification is observed to regulate microglia’s inflammatory processes ( Zhang F. et al, 2022 ). Studies suggest that METTL3 promotes lipopolysaccharide (LPS)-induced microglial inflammation by activating the TNF receptor associated factor 6 (TRAF6)-NF-κB pathway ( Wen et al, 2022 ) and improves neuronal apoptosis and microglial activation by inactivating MyD88/NF-κB pathway ( Chen Y. et al, 2022 ).…”