Science advances

Neuron-produced SPP1 signals microglia to reduce brain cell damage

Updated

Abstract

Neuron-derived SPP1 is associated with enhanced microglial activity and neuronal survival in neurodegenerative conditions.

  • SPP1 reprograms microglia into a neuroprotective state after injury and during neurodegeneration.
  • In mouse models, SPP1 enhances microglial functions like debris clearance and anti-inflammatory responses.
  • Elevated levels of SPP1 are found in neurons of glaucomatous retinas, correlating with increased cell resilience.
  • In Alzheimer's disease, neuronal SPP1 levels correlate with neuronal survival, while microglia near amyloid plaques show impaired function.
  • SPP1 promotes microglial clearance of amyloid beta in human cell cultures, potentially preventing neurodegeneration.

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