Microglial lactate metabolism as a potential therapeutic target for Alzheimer's disease

• Published in: Molecular neurodegeneration Vol. 17; no. 1; p. 36
• Main Authors: Zhao, Yingjun, Xu, Huaxi
• Format: Journal Article
• Language: English
• Published: England BioMed Central 12.05.2022; BMC
• Subjects: Alzheimer's disease; Energy metabolism; Epigenetics; Feedback; Gene expression; Glucose; Glucose metabolism; Glycolysis; Histone H4; Immune clearance; Inflammation; Lactic acid; Lysine; Metabolic disorders; Microglia; Neurodegenerative diseases; Parkinson's disease; Pathogenesis; Phagocytes; Phagocytosis; Phosphorylation; Research Highlight; Therapeutic targets; Trends
• ISSN: 1750-1326; 1750-1326
• DOI: 10.1186/s13024-022-00541-z

Sustained activation of glycolytic metabolism would lead to low efficiency of ATP production and compromise of microglial immune functions [9]. Since the energy metabolism is required for Aβ phagocytosis and clearance, the low efficiency of ATP production due to glycolytic metabolism would impair the phagocytic function of microglia and result in Aβ accumulation. In summary, this study highlights a crosstalk between lactate metabolism and histone lactylation in microglia, and reveals how this lactate-derived epigenetic modification exacerbates microglial dysfunction and neuroinflammation in the development and progression of AD. [...]targeting lactate metabolism disorder may represent a novel strategy for AD intervention (Fig. 1). Positive feedback regulation of microglial glucose metabolism by histone H4 lysine 12 lactylation in Alzheimer's disease.