TBK1 Deficiency Disrupts Microglial Metabolic Reprogramming, Promoting Glycolytic SASP in ALS

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TBK1 loss-of-function mutations in ALS disrupt microglial metabolic homeostasis by impairing mTOR-dependent metabolic checkpoint signaling and mitochondrial quality control. Under normal conditions, TBK1 phosphorylates ULK1 and AMPK to coordinate autophagy-mediated mitochondrial turnover with oxidative metabolism, enabling microglia to maintain anti-inflammatory M2 polarization. In ALS patients wi