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From lactate to lactylation: novel pathological mechanisms and potential therapeutic targets for high-altitude cerebral oedema
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DOI：10.1017/erm.2026.10046.png)
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Abstract
En 中文
BackgroundHigh altitude cerebral edema (HACE); a fatal terminal stage of acute mountain sickness (AMS); is triggered by rapid exposure to hypoxia at high altitudes. The pathophysiology of HACE is complex; involving multiple key processes including energy metabolism disorders; oxidative stress; blood-brain barrier (BBB) injury; and neuroinflammation; all of which interact to drive disease progression. Lactylation; a novel epigenetic regulatory mechanism discovered in 2019; provides a fresh perspective for HACE research.MethodsThis study integrates the latest research findings on the pathophysiology of HACE; lactate metabolism; and the role of lactylation in hypoxia-related diseases (such as cancer and ischemic-hypoxic diseases). It focuses on analyzing the potential molecular mechanisms of lactylation in HACE; including its regulation of the HIF-1α/NF-κB axis; inflammation; and metabolism; and discusses existing lactylation regulation strategies.ResultsIn HACE; hypoxia-driven glycolysis elevates lactate; promoting protein lactylation (e.g.; NuRD complex in microglia; which is correlated with proinflammatory cytokines). Lactylation may regulate HIF-1α/NF-κB axis; inflammation; and metabolism in HACE pathogenesis. Currently; methods such as the inhibition of lactate dehydrogenase (LDH) /monocarboxylate transporters and the use of histone deacetylase inhibitors have been proven effective in regulating lactylation.ConclusionLactylation is a key link connecting metabolic disorders and neuroinflammation in HACE. However; the dual role of lactate in neuroprotection and neuroinjury under hypoxic conditions still requires further exploration. Future research should focus on deciphering the molecular networks related to HACE and developing precise intervention strategies to provide new directions for HACE treatment.
Keywords:
high-altitude cerebral oedema
lactate
lactylation
neuroinflammation
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