Titre :

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

Auteur(s) :

Zhang, Zui [Auteur]
Nagoya University
Takeda-Uchimura, Yoshiko [Auteur]
Nagoya University
Foyez, Tahmina [Auteur]
Nagoya University
Ohtake-Niimi, Shiori [Auteur]
Nagoya University
Narentuya, null [Auteur]
Nagoya University
Akatsu, Hiroyasu [Auteur]
Toyohashi University of Technology [TUT]
Nishitsuji, Kazuchika [Auteur]
Tokushima University
Michikawa, Makoto [Auteur]
Nagoya University
Wyss-Coray, Tony [Auteur]
Stanford Medicine
Kadomatsu, Kenji [Auteur]
Nagoya University
Uchimura, Kenji [Auteur]
Nagoya University

Titre de la revue :

Proceedings of the National Academy of Sciences of the United States of America

Nom court de la revue :

Proc. Natl. Acad. Sci. U.S.A.

Numéro :

114

Pagination :

E2947-E2954

Date de publication :

2017

ISSN :

1091-6490

Mot(s)-clé(s) en anglais :

Alzheimer’s disease
Humans
Male
Mice, Transgenic
Alzheimer Disease
N-Acetylneuraminic Acid
Keratan Sulfate
Microglia
Sialic Acid
Plaque, Amyloid
Animals
Sulfotransferase
carbohydrate-recognizing receptors
Aged, 80 and over
Female
Polysaccharide
Phagocytosis
Amyloid beta-Protein Precursor
Disease Models, Animal

Discipline(s) HAL :

Chimie/Chimie théorique et/ou physique

Résumé en anglais : [en]

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 ...
Lire la suite >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.Lire moins >

Langue :

Anglais

Audience :

Non spécifiée

Établissement(s) :

CNRS
Université de Lille

Collections :

• Autres travaux scientifiques

Date de dépôt :

2020-02-12T15:11:34Z
2021-03-25T08:26:01Z