ALKBH5 demethylates the m⁶A modification of SOCS3 in microglia/macrophages and alleviates neuroinflammation after brain injury.

ABSTRACT: Microglia/macrophage-induced neuroinflammation plays a crucial role in the progression of traumatic brain injury (TBI). However, the involvement of N6-methyladenosine (m⁶A) RNA modifications in this process remains elusive. Single-cell RNA sequencing (scRNA-seq) and m⁶A RNA immunoprecipitation sequencing (MeRIP-seq) across multiple time points postinjury revealed a strong correlation between m⁶A modifications and genes enriched in microglia/macrophages. Furthermore, the m⁶A demethylase ALKBH5 was identified as a key regulator of dynamic m⁶A patterns at the injury site. ALKBH5 suppression in microglia/macrophages exacerbated neuroinflammation in vitro and worsened neurological deficits in controlled cortical impact (CCI) models. MeRIP-q

SUBMITTER: Cai L 

PROVIDER: S-EPMC12501137 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature