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Article Dans Une Revue Proceedings of the National Academy of Sciences of the United States of America Année : 2017

Deficiency of a sulfotransferase for sialic acid-modified glycans mitigates Alzheimer's pathology

Résumé

We previously showed that microglial keratan sulfate (KS) was induced in amyotrophic lateral sclerosis. However, the functional roles of the glycan and its synthetic enzyme in neurodegenerative diseases, such as Alzheimer's disease (AD), a progressive disorder, are unclear. In our study, KS modified with sialic acids having a molecular mass of 125-220 kDa and the carbohydrate sulfotransferase GlcNAc6ST1 were up-regulated in the brains of two transgenic mouse models (J20 and Tg2576) and the brains of patients with AD. GlcNAc6ST1-deficient J20 (J20/GlcNAc6ST1-/-) mice demonstrated a complete absence of the microglial sialylated KS. J20/GlcNAc6ST1-/- primary microglia showed an increased level of amyloid-β phagocytosis and were hyperresponsive to interleukin 4, a potent antiinflammatory cytokine. Moreover, J20/GlcNAc6ST1-/- mice manifested reduced cerebral amyloid-β deposition. GlcNAc6ST1-synthesizing sialylated KS thus modulates AD pathology. Inhibition of KS synthesis by targeting GlcNAc6ST1 may therefore be beneficial for controlling AD pathogenesis.

Dates et versions

hal-03180438 , version 1 (25-03-2021)

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Citer

Zui Zhang, Yoshiko Takeda-Uchimura, Tahmina Foyez, Shiori Ohtake-Niimi, Null Narentuya, et al.. Deficiency of a sulfotransferase for sialic acid-modified glycans mitigates Alzheimer's pathology. Proceedings of the National Academy of Sciences of the United States of America, 2017, Proceedings of the National Academy of Sciences of the United States of America, 114 (14), pp.E2947-E2954. ⟨10.1073/pnas.1615036114⟩. ⟨hal-03180438⟩

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