Translational control of microglial metabolism, inflammatory responses, and survival by the eIF4E-binding proteins.

Elevated cerebrospinal fluid 4E-BP1 levels in Alzheimer’s disease are linked to increased microglial mitochondrial biogenesis and reduced inflammation.

• Why it matters: Understanding how mTOR pathway effectors influence microglial responses is crucial for developing therapies for AD, as microglial dysfunction contributes to disease progression.
• What they did: The study used in vitro experiments and linear regression analysis of CSF samples to investigate the role of 4E-BP1/2, revealing that amyloid-β inactivates 4E-BP1 via SYK-mTORC1 signaling, and deletion of 4E-BP1/2 enhances mitochondrial function and protects microglia from apoptosis.
• The result: Disruption of 4E-BP1 inactivation impairs immune resolution, causes metabolic exhaustion, and promotes microglial cell death, highlighting the SYK-mTORC1-4E-BP1 axis as a key regulator in AD microglial metabolism and survival.