Neuron-derived SPP1 instructs microglia to limit degeneration.

Authors

Song Li, Tatjana C Jakobs

Published in

Science advances. Volume 12. Issue 35. Pages eaee4940. Aug 28, 2026. Epub Aug 28, 2026.

Abstract

Neurons actively shape immune responses that maintain central nervous system integrity. We identify SPP1 (secreted phosphoprotein 1) as a neuron-derived signal that reprograms microglia into a neuroprotective, homeostatic state after injury and during neurodegeneration. In mouse models of glaucoma and optic nerve damage, neuronal SPP1 enhances microglial autophagy, debris clearance, and anti-inflammatory activity, preserving neuronal survival and visual function. SPP1 is elevated in neurons of human and primate glaucomatous retinas, where SPP1⁺ cells show increased resilience. In Alzheimer's disease brain, neuronal SPP1 correlates with neuronal survival, while microglia around Aβ plaques display defective autophagy. In human iPSC co-cultures, SPP1 enhances microglial Aβ clearance and prevents neurodegeneration. Thus, SPP1 defines a protective neuron-microglia axis in glaucoma and possibly other neurodegenerative diseases.

PMID:
42664340
Bibliographic data and abstract were imported from PubMed on 29 Aug 2026.

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