Secreted GPNMB enhances uptake of fibrillar alpha-synuclein in a non-cell-autonomous process that can be blocked by anti-GPNMB antibodies.

Extracellular GPNMB promotes alpha-synuclein uptake in Parkinson's disease models, with higher GPNMB expression linked to more widespread pathology in humans.

• Why it matters: Understanding how GPNMB influences alpha-synuclein spread is crucial because it may reveal targets to halt neurodegeneration in Parkinson's disease, which currently lacks disease-modifying treatments.
• What they did: The study examined GPNMB's role using human brain tissue, induced pluripotent stem cell-derived microglia, and a fibril-seeded Parkinson's model, showing that GPNMB enhances alpha-synuclein uptake and pathology.
• The result: Blocking GPNMB with antibodies reduces neuronal alpha-synuclein accumulation, suggesting that targeting GPNMB could interrupt the cycle of neurodegeneration and serve as a potential therapeutic strategy.