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RUVBL2 Regulates Microglia Metabolic Reprogramming to Mediate Stress Granules Aggregation Exacerbating Postoperative
Lin Zhang1,2,3,4, Zixuan Wang1, Chenyi Yang2,3
1The Third Central Clinical College of Tianjin Medical University, Tianjin, China.
Aging Cell
|April 3, 2026
Summary
Postoperative delirium (POD) accelerates cognitive decline. RUVBL2 promotes microglial metabolic reprogramming, worsening POD. Inhibiting RUVBL2 may offer a new therapeutic strategy for POD and Alzheimer's disease progression.
Area of Science:
- Neuroscience
- Immunology
- Metabolic Research
Background:
- Postoperative delirium (POD) exacerbates mild cognitive impairment (MCI) to Alzheimer's disease (AD) transition in elderly patients.
- Microglial metabolic reprogramming is crucial in neuroinflammation and cognitive function post-surgery.
- RUVBL2 overexpression disrupts metabolic balance, causing stress granule (SG) aggregation and fibrosis.
Purpose of the Study:
- Investigate RUVBL2's role in microglial metabolic reprogramming and SG formation.
- Identify RUVBL2 as a prognostic target to inhibit glycolysis and mitigate POD-induced MCI progression.
Main Methods:
- Established a POD model in aged MCI rats using sevoflurane anesthesia and orthopedic surgery.
- Assessed cognitive function using multimodal magnetic resonance imaging (MRI).
- Quantified microglial metabolic activity (glycolysis and OXPHOS) via ECAR and OCR; modulated RUVBL2 expression using lentivirus.
Main Results:
- Postoperative microglia shifted from OXPHOS to glycolysis, with RUVBL2 levels correlating positively with POD.
- Elevated RUVBL2 drove metabolic reprogramming; RUVBL2 knockdown reversed this, reducing neuroinflammation and SG aggregation.
- RUVBL2 knockdown improved cognitive deficits and neural activity, enhancing OXPHOS and reducing glycolysis in microglia.
Conclusions:
- RUVBL2 critically regulates POD by driving microglial metabolic reprogramming.
- Metabolic reprogramming presents a novel therapeutic target for POD.
- RUVBL2 is a potential intervention target for mitigating POD and its progression to cognitive impairment.
