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

2026-01-28 neurology Title + abstract only
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Glycoprotein nonmetastatic melanoma B (GPNMB), encoded by the target gene (GPNMB) of a Parkinsons disease (PD) risk locus, acts as a secreted factor mediating inflammatory effects in the context of immunity and cancer. In a neurodegenerative disease context, GPNMB is critical to cellular uptake of pathological forms of alpha-synuclein (aSyn), the hallmark disease protein that misfolds and accumulates in PD. Here, we demonstrate that the non-membrane-anchored, extracellular domain of GPNMB, shed ...

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