ArticlePloS one2013
Ablation of keratan sulfate accelerates early phase pathogenesis of ALS.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 46 citations in OpenAlex.
- Keratan Sulfate Is a Multifunctional Brain Glycosaminoglycan With Instructive Capabilities.Journal of neurochemistry · 2025Review
- Circular RNA expression in ALS is progressively deregulated and tissue-dependent.BMC genomics · 2025Article
- A Biomimetic Synthetic Strategy Can Provide Keratan Sulfate I and II Oligosaccharides with Diverse Fucosylation and Sulfation Patterns.Journal of the American Chemical Society · 2024Article
- Microglia heterogeneity in health and disease.FEBS open bio · 2024Review
- Recent Advances in Microglia Modelling to Address Translational Outcomes in Neurodegenerative Diseases.Cells · 2022Review
- Beta3Gn-T7 Is a Keratan Sulfate β1,3Frontiers in neuroanatomy · 2022Article
- Multifaceted microglia - key players in primary brain tumour heterogeneity.Nature reviews. Neurology · 2021Review
- Analysis of circulating protein aggregates as a route of investigation into neurodegenerative disorders.Brain communications · 2021Article
- Novel Insight Into the Role of Immune Dysregulation in Amyotrophic Lateral Sclerosis Based on Bioinformatic Analysis.Frontiers in neuroscience · 2021Article
- Glycosaminoglycans in Neurodegenerative Diseases.Advances in experimental medicine and biology · 2021Review
- Galectins and Their Ligand Glycoconjugates in the Central Nervous System Under Physiological and Pathological Conditions.Frontiers in neuroanatomy · 2021Review
- Recent Advances in Applications of Bioactive Egg Compounds in Nonfood Sectors.Frontiers in bioengineering and biotechnology · 2021Review
- Microglial subtypes: diversity within the microglial community.The EMBO journal · 2019Review
- Role of keratan sulfate expression in human pancreatic cancer malignancy.Scientific reports · 2019Article
- Software for Peak Finding and Elemental Composition Assignment for Glycosaminoglycan Tandem Mass Spectra.Molecular & cellular proteomics : MCP · 2018Article
- Review
- Sulfated glycosaminoglycans in protein aggregation diseases.Glycoconjugate journal · 2017Review
- 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 · 2017Article
- Keratan sulfate glycosaminoglycan from chicken egg white.Glycobiology · 2016Article
- Keratan Sulfate Regulates the Switch from Motor Neuron to Oligodendrocyte Generation During Development of the Mouse Spinal Cord.Neurochemical research · 2016Article
Corrections and comments
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Authors and funding
16 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Biopolymers consist of three major classes, i.e., polynucleotides (DNA, RNA), polypeptides (proteins) and polysaccharides (sugar chains). It is widely accepted that polynucleotides and polypeptides play fundamental roles in the pathogenesis of neurodegenerative diseases. But, sugar chains have been poorly studied in this process, and their biological/clinical significance remains largely unexplored. Amyotrophic lateral sclerosis (ALS) is a motoneuron-degenerative disease, the pathogenesis of which requires both cell autonomous and non-cell autonomous processes. Here, we investigated the role of keratan sulfate (KS), a sulfated long sugar chain of proteoglycan, in ALS pathogenesis. We employed ALS model SOD1(G93A) mice and GlcNAc6ST-1(-/-) mice, which are KS-deficient in the central nervous system. Unexpectedly, SOD1(G93A)GlcNAc6ST-1(-/-) mice exhibited a significantly shorter lifespan than SOD1(G93A) mice and an accelerated appearance of clinical symptoms (body weight loss and decreased rotarod performance). KS expression was induced exclusively in a subpopulation of microglia in SOD1(G93A) mice, and became detectable around motoneurons in the ventral horn during the early disease phase before body weight loss. During this phase, the expression of M2 microglia markers was transiently enhanced in SOD1(G93A) mice, while this enhancement was attenuated in SOD1(G93A)GlcNAc6ST-1(-/-) mice. Consistent with this, M2 microglia were markedly less during the early disease phase in SOD1(G93A)GlcNAc6ST-1(-/-) mice. Moreover, KS expression in microglia was also detected in some human ALS cases. This study suggests that KS plays an indispensable, suppressive role in the early phase pathogenesis of ALS and may represent a new target for therapeutic intervention.
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