Fig. 8
Pathological mechanisms of the interaction between lactate metabolism disorders and neuroinflammation in the SCZ brain. Abnormal activation of microglia in SCZ can trigger the activation of NLRP3 inflammasomes. Additionally, the abnormal accumulation of lactate in these cells can activate NLRP3 inflammasomes through protein kinase R phosphorylation (p-PKR). In SCZ neuronal cells, excessive lactate accumulation can lead to NLRP3 activation via histone lactylation, facilitated by LDHA. Mitochondrial dysfunction in SCZ induces oxidative stress and activates neuroinflammation, which damages neurons and astrocytes. This damage further disrupts lactate metabolism. Microglial activation also increases astrocyte activity, contributing to central nervous system damage. This process represents a dynamic progression from compensation to decompensation20,70,79,82. This figure was created by Figdraw2.0, https://www.figdraw.com.
