Lactylation (Kla) represents a post-translational modification linking glycolytic flux to chromatin and protein function, with implications for neuroinflammation. In the CNS, lactate production, compartmentalization, and transport are governed by cell-type–specific expression of lactate dehydrogenases and monocarboxylate transporters within the neurovascular unit, creating dynamic microenvironments that influence inflammatory tone.
Kla has been observed on histone and non-histone substrates and is implicated in reprogramming inflammatory and stress-response networks across microglia, astrocytes, endothelial cells, and neurons. These effects intersect with canonical pathways including NF-κB, inflammasome signaling, and cytokine-driven transcriptional programs.
Gaps remain in defining Kla machinery (writers, erasers, readers), clarifying how lactate flux quantitatively relates to site-specific lactylation, and understanding context dependence across disease stage, cell state, and brain region. The current view integrates CNS lactate metabolism with Kla biology, drawing evidence from acute injury and neurodegeneration.
Priority areas include causal mapping, biomarker development, and time-windowed, cell-targeted strategies to mitigate maladaptive inflammation while preserving repair processes.
These features generate evolving microenvironments that influence neuroinflammatory tone.