Keywords
Elderly
Pyruvate kinase M2
Metabolic reprogramming
Targeted therapy
Published : 2026-08-12
Abstract
Perioperative Neurocognitive Disorders (PND) are common postoperative complications affecting cognitive and behavioral function in elderly patients, significantly impacting recovery quality. Its pathogenesis is closely linked to an imbalance in cerebral metabolic-immune homeostasis. Recent studies have identified the key metabolic and immune enzyme, Pyruvate Kinase M2 (PKM2), as a participant in the initiation and progression of PND. Surgical trauma and anesthesia can upregulate PKM2 via signaling pathways such as HMGB1, TLR4, and HIF-1α, promoting its acetylation, dimerization, and nuclear translocation. Subsequently, activated PKM2 enhances oxidative stress and recruits NLRPs to drive neuroinflammation and synaptic plasticity decline, leading to postoperative cognitive dysfunction. These cascading changes, to a certain extent, affect postoperative neurological recovery. Mouse model studies have revealed therapeutic strategies targeting PKM2. This review summarizes the mechanisms by which PKM2 influences cognitive and behavioral function through the regulation of neuroinflammation and energy metabolism disorders, and discusses precise brain protection strategies targeting PKM2, offering new insights for the prevention and treatment of PND.
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