Microglial keratan sulfate epitope elicits ...
Document type :
Article dans une revue scientifique
PMID :
Permalink :
Title :
Microglial keratan sulfate epitope elicits in central nervous tissues of transgenic model mice and patients with amyotrophic lateral sclerosis
Author(s) :
Foyez, Tahmina [Auteur]
Takeda-Uchimura, Yoshiko [Auteur]
Ishigaki, Shinsuke [Auteur]
Narentuya, null [Auteur]
Zhang, Zui [Auteur]
Sobue, Gen [Auteur]
Kadomatsu, Kenji [Auteur]
Uchimura, Kenji [Auteur]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Takeda-Uchimura, Yoshiko [Auteur]
Ishigaki, Shinsuke [Auteur]
Narentuya, null [Auteur]
Zhang, Zui [Auteur]
Sobue, Gen [Auteur]
Kadomatsu, Kenji [Auteur]
Uchimura, Kenji [Auteur]

Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Journal title :
The American journal of pathology
Abbreviated title :
Am. J. Pathol.
Volume number :
185
Pages :
3053-3065
Publication date :
2015-11
ISSN :
1525-2191
English keyword(s) :
Brain
Humans
Middle Aged
Mice, Inbred C57BL
Male
Mice, Transgenic
Epitopes
Mutation, Missense
Keratan Sulfate
Microglia
Animals
Amyotrophic Lateral Sclerosis
Spinal Cord
Sulfotransferase
Aged, 80 and over
Motor Neurons
Galectin 3
Female
Mice
Aged
Disease Models, Animal
Superoxide Dismutase
Humans
Middle Aged
Mice, Inbred C57BL
Male
Mice, Transgenic
Epitopes
Mutation, Missense
Keratan Sulfate
Microglia
Animals
Amyotrophic Lateral Sclerosis
Spinal Cord
Sulfotransferase
Aged, 80 and over
Motor Neurons
Galectin 3
Female
Mice
Aged
Disease Models, Animal
Superoxide Dismutase
HAL domain(s) :
Chimie/Chimie théorique et/ou physique
English abstract : [en]
The functional role of 5D4 antibody-reactive keratan sulfate (KS) in the pathogenesis of neurodegenerative diseases is unknown. We therefore studied the expression of 5D4-reactive KS in amyotrophic lateral sclerosis (ALS), ...
Show more >The functional role of 5D4 antibody-reactive keratan sulfate (KS) in the pathogenesis of neurodegenerative diseases is unknown. We therefore studied the expression of 5D4-reactive KS in amyotrophic lateral sclerosis (ALS), a motor neuron-degenerative disease, with the use of SOD1(G93A) ALS model mice and patients with ALS. Histochemical and immunoelectron microscopic characterizations showed that the 5D4-reactive KS is expressed in Mac2/galectin-3-positive activated or proliferating microglia of SOD1(G93A) ALS model mice at disease end stage and that the KS is an O-linked glycan modified with sialic acid and fucose, which was thus far shown to exist in cartilage. Intriguingly, microglial KS was detected in the spinal cord and brainstem but not in the cerebral cortex of SOD1(G93A) mice. We found that KSGal6ST, a galactose-6-sulfotransferase, is required for biosynthesis of the microglial 5D4-reactive KS by generating SOD1(G93A)/KSGal6ST(-/-) mice. The requirement of GlcNAc6ST1 for this synthesis was corroborated by analyzing SOD1(G93A)/GlcNAc6ST1(-/-) mice. These results indicate that both galactose-6- and N acteylglucosamine-6-sulfated KS elicited in the spinal cord and brainstem are associated with the degeneration of spinal and bulbar lower motor neurons in ALS pathology and may play a role in disease progression via microglial activation and proliferation.Show less >
Show more >The functional role of 5D4 antibody-reactive keratan sulfate (KS) in the pathogenesis of neurodegenerative diseases is unknown. We therefore studied the expression of 5D4-reactive KS in amyotrophic lateral sclerosis (ALS), a motor neuron-degenerative disease, with the use of SOD1(G93A) ALS model mice and patients with ALS. Histochemical and immunoelectron microscopic characterizations showed that the 5D4-reactive KS is expressed in Mac2/galectin-3-positive activated or proliferating microglia of SOD1(G93A) ALS model mice at disease end stage and that the KS is an O-linked glycan modified with sialic acid and fucose, which was thus far shown to exist in cartilage. Intriguingly, microglial KS was detected in the spinal cord and brainstem but not in the cerebral cortex of SOD1(G93A) mice. We found that KSGal6ST, a galactose-6-sulfotransferase, is required for biosynthesis of the microglial 5D4-reactive KS by generating SOD1(G93A)/KSGal6ST(-/-) mice. The requirement of GlcNAc6ST1 for this synthesis was corroborated by analyzing SOD1(G93A)/GlcNAc6ST1(-/-) mice. These results indicate that both galactose-6- and N acteylglucosamine-6-sulfated KS elicited in the spinal cord and brainstem are associated with the degeneration of spinal and bulbar lower motor neurons in ALS pathology and may play a role in disease progression via microglial activation and proliferation.Show less >
Language :
Anglais
Administrative institution(s) :
CNRS
Université de Lille
Université de Lille
Submission date :
2020-02-12T15:11:38Z