H3K14 lactylation exacerbates neuronal ferroptosis by inhibiting calcium efflux following intracerebral hemorrhagic stroke

-ATPase PMCA2 encoding gene as a direct downstream target of H3K14la. H3K14la/PMCA2 promoted ferroptosis by elevating intracellular calcium levels. In line with our in vitro findings, inhibiting H3K14la/PMCA2 reduced neuronal degeneration and improved functional outcomes in an ICH mouse model induced by intracranial injection of collagenase into the striatum. Taken together, our findings elucidate the role of histone lactylation and PMCA2 in neuronal ferroptosis and implicate that targeting histone lactylation could be a promising therapeutic strategy for ICH and related CNS diseases.