Fig. 1
From: Microglial lactate metabolism as a potential therapeutic target for Alzheimer’s disease
Lactate metabolism disorder in microglia of Alzheimer’s disease. Under the healthy condition, microglia maintain the homeostasis of lactate metabolism. Along with aging or AD development, microglia up-regulate glycolytic machinery and switch metabolism from OXPHOS to aerobic glycolysis, resulting in lactate accumulation and histone hyperlactylation. On the one hand, lactate is released to the extracellular through monocarboxylate transporters (MCTs) and affects the acidity of microenvironment, leading to neuronal damage; on the other hand, lactate is transported to the nuclei and leads to histone lactylation in turn promotes glycolytic activity through transcriptional activation of glycolytic genes, thus exacerbating lactate metabolism disorder and neuroinflammation during AD pathogenesis