Sialic acid-binding Ig-like lectin (Siglec) receptors are linked to neurodegenerative processes, but the role of sialic acids in physiological aging is still not fully understood. We investigated the impact of reduced sialylation in the brain of mice heterozygous for the enzyme glucosamine-2-epimerase/N-acetylmannosamine kinase (GNE+/-) that is essential for sialic acid biosynthesis. We demonstrate that GNE+/- mice have hyposialylation in different brain regions, less synapses in the hippocampus and reduced microglial arborization already at 6 months followed by increased loss of neurons at 12 months. A transcriptomic analysis revealed no pro-inflammatory changes indicating an innate homeostatic immune process leading to the removal of synapses and neurons in GNE+/- mice during aging. Crossbreeding with complement C3-deficient mice rescued the earlier onset of neuronal and synaptic loss as well as the changes in microglial arborization. Thus, sialic acids of the glycocalyx contribute to brain homeostasis and act as a recognition system for the innate immune system in the brain.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.neurobiolaging.2020.01.008 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Metastasis is the leading cause of mortality in breast cancer, with lung metastasis being particularly detrimental. Identification of the processes determining metastatic organotropism could enable the development of approaches to prevent and treat breast cancer metastasis. Here, we found that lung-tropic and non-lung-tropic breast cancer cells differ in their response to sialic acids, affecting the sialylation of surface proteins.
View Article and Find Full Text PDFThe apolipoprotein E ( ) ε4 allele is the strongest genetic risk factor for Alzheimer's disease (AD). ApoE is glycosylated with an O-linked Core-1 sialylated glycan at several sites, yet the impact and function of this glycosylation on AD biomarkers remains unclear. We examined apoE glycosylation in a cohort of cerebrospinal fluid (CSF, n=181) and plasma (n= 178) samples from the Alzheimer's Disease Neuroimaging Initiative (ADNI) stratified into 4 groups: cognitively normal (CN), Mild Cognitive Impairment (MCI), progressors and non-progressors based on delayed word recall performance over 4 years.
View Article and Find Full Text PDFStructure-Function Relationships of the CMP-Sialic Acid Transporter through Analysis of a Pathogenic Variant in an Alternatively Spliced Functional Isoform.
ACS Omega
December 2024
Laboratorio de Glicobiología y Diagnóstico Molecular, Centro de Investigación en Dinámica Celular, Universidad Autónoma del Estado de Morelos, Av. Universidad 1001, Col. Chamilpa, Cuernavaca 62209, Morelos, México.
The human CMP-sialic acid transporter (hCST) is a mammalian highly conserved type III antiporter that translocates CMP-sialic acid into the Golgi lumen, supporting sialylation. Although different works have focused on elucidating structure-function relationships in the hCST, this is the first study to address them in an alternatively spliced isoform. We have previously reported the expression of a functional human del177 isoform that has skipping of exon 6, resulting in a loss of 59 amino acids, without change in the open reading frame and conserving its C-terminal region.
View Article and Find Full Text PDFA mucus layer derived from porcine intestinal organoid air-liquid interface monolayer attenuates swine enteric coronavirus infection by antiviral activity of Muc2.
BMC Biol
December 2024
State Key Laboratory for Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou University, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, China.
Background: The mucus layer provides the first defense that keeps the epithelium free from microorganisms. However, the effect of the small intestinal mucus layer on pathogen invasion is still poorly understood, especially for swine enteric coronavirus. To better understand virus‒mucus layer‒intestinal epithelium interactions, here, we developed a porcine intestinal organoid mucus‒monolayer model under air‒liquid interface (ALI) conditions.
View Article and Find Full Text PDFGolgi pH elevation due to loss of V-ATPase subunit V0a2 function correlates with tissue-specific glycosylation changes and globozoospermia.
Cell Mol Life Sci
December 2024
Institute of Human Genetics, University Medical Center Göttingen, 37073, Göttingen, Germany.
Loss-of-function variants in ATP6V0A2, encoding the trans Golgi V-ATPase subunit V0a2, cause wrinkly skin syndrome (WSS), a connective tissue disorder with glycosylation defects and aberrant cortical neuron migration. We used knock-out (Atp6v0a2) and knock-in (Atp6v0a2) mice harboring the R755Q missense mutation selectively abolishing V0a2-mediated proton transport to investigate the WSS pathomechanism. Homozygous mutants from both strains displayed a reduction of growth, dermis thickness, and elastic fiber formation compatible with WSS.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!