imprint:
Proceedings of the National Academy of Sciences, 2017
Published in:Proceedings of the National Academy of Sciences
Language:
English
DOI:
10.1073/pnas.1615036114
ISSN:
0027-8424;
1091-6490
Origination:
Footnote:
Description:
<jats:title>Significance</jats:title>
<jats:p>Keratan sulfate (KS) is an extracellular sulfated glycan covalently attached to core proteins in the brain. Here, we show that a type of KS with a certain molecular mass in microglia and its synthetic enzyme GlcNAc6ST1, previously known as a sulfotransferase for ligands of L-selectin, are upregulated in model mice and patients with Alzheimer’s disease. GlcNAc6ST1 deficiency resulted in increased amyloid-β phagocytosis and hyperresponsiveness to an antiinflammatory cytokine in primary microglia. Moreover, amyloid-β pathology was mitigated in GlcNAc6ST1-deficient Alzheimer’s model mice. These data support a model in which GlcNAc6ST1 regulates microglial functions via synthesizing sialic acid-modified KS, a potential ligand for microglial carbohydrate-recognizing receptors, in Alzheimer’s pathology.</jats:p>