Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

L-Fucose is a candidate monosaccharide neuromodulator and mitigates Alzheimer’s synaptic deficits II

ABSTRACT: Fucosylation, a major glycan modification, has been shown to influence neuronal and microglial mechanisms, but whether unconjugated free L-fucose can impact brain function is unknown. L-fucose can be transported into cells and metabolized by fucokinase (FCSK) via the poorly understood salvage pathway. Using mouse hippocampal slices, we showed that L-fucose enhanced excitatory neurotransmission and long-term potentiation (LTP) through regulation of pre-synaptic release. Such effects required L-fucose metabolism through the FCSK-driven salvage pathway and were not likely dependent on fucosylation, suggesting a metabolic-signaling mechanism. Human Alzheimer’s disease (AD) and 5xFAD mouse brains showed signs of fucose hypometabolism with impaired L-fucose signaling. Such abnormalities were corrected by exogenous L-fucose, exemplified by rectification of LTP deficits in 5xFAD hippocampus. Dietary L-fucose supplement, which increased cerebral free L-fucose levels and upregulated FCSK to drive the salvage pathway, mitigated synaptic and behavioral deficits of 5xFAD mice. Our data suggests an unrecognized neuromodulatory function of free L-fucose and reveals its therapeutic potential for AD.

ORGANISM(S): Mus musculus

PROVIDER: GSE295460 | GEO | 2025/12/04

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

L-Fucose is a candidate monosaccharide neuromodulator and mitigates Alzheimer’s synaptic deficits

Project description:Fucosylation, a major glycan modification, has been shown to influence neuronal and microglial mechanisms, but whether unconjugated free L-fucose can impact brain function is unknown. L-fucose can be transported into cells and metabolized by fucokinase (FCSK) via the poorly understood salvage pathway. Using mouse hippocampal slices, we showed that L-fucose enhanced excitatory neurotransmission and long-term potentiation (LTP) through regulation of pre-synaptic release. Such effects required L-fucose metabolism through the FCSK-driven salvage pathway and were not likely dependent on fucosylation, suggesting a metabolic-signaling mechanism. Human Alzheimer’s disease (AD) and 5xFAD mouse brains showed signs of fucose hypometabolism with impaired L-fucose signaling. Such abnormalities were corrected by exogenous L-fucose, exemplified by rectification of LTP deficits in 5xFAD hippocampus. Dietary L-fucose supplement, which increased cerebral free L-fucose levels and upregulated FCSK to drive the salvage pathway, mitigated synaptic and behavioral deficits of 5xFAD mice. Our data suggests an unrecognized neuromodulatory function of free L-fucose and reveals its therapeutic potential for AD.

2025-12-04 | GSE295285 | GEO

Gene expression profiling of fucose-deficient Fx-/- mice cDC1-enriched splenocytes

Project description:Analysis of the top differentially regulated genes in cDC1 in response to fucose treatment revealed genes enriched in pathways such as immune-effector processes, myeloid leukocyte activation, exocytosis, and secretion. We used microarrays to detail the global programme of gene expression underlying fucosylation deficiency in mouse cDC1 cells

2021-03-10 | GSE163958 | GEO

L-Fucose is a candidate monosaccharide neuromodulator and mitigates Alzheimer’s synaptic deficits

Project description:L-Fucose is a candidate monosaccharide neuromodulator and mitigates Alzheimer’s synaptic deficits

| PRJNA1254119 | ENA

A TrkB and TrkC partial agonist prevents synaptic plasticity deficits and elicits activity-dependent synaptic and microglial transcriptomic changes in a late-stage Alzheimer’s disease mouse model

Project description:Introduction: TrkB and TrkC receptor signaling promotes synaptic plasticity and interacts with pathways affected by amyloid-β (Aβ)-toxicity. Upregulating TrkB/C signaling could reduce Alzheimer’s disease (AD)-related degenerative signaling, memory loss, and synaptic dysfunction. Methods: PTX-BD10-2 (BD10-2), a small molecule TrkB/C receptor partial agonist, was orally administered to aged London/Swedish-APP mutant mice (APPL/S) and wild-type controls (WT). Effects on memory and hippocampal long-term potentiation (LTP) were assessed using electrophysiology, behavioral studies, immunoblotting, immunofluorescence staining, and RNA-sequencing. Results: Memory and LTP deficits in APPL/S mice were attenuated by treatment with BD10-2. BD10-2 prevented aberrant AKT, CaMKII, and GLUA1 phosphorylation, and enhanced activity-dependent recruitment of synaptic proteins. BD10-2 also had potentially favorable effects on LTP-dependent complement pathway and synaptic gene transcription. Conclusions: BD10-2 prevented APPL/S/Aβ-associated memory and LTP deficits, reduced abnormalities in synapse-related signaling and activity-dependent transcription of synaptic genes, and bolstered transcriptional changes associated with microglial immune response.

2025-09-11 | GSE243110 | GEO

Microglial repopulation reverses cognitive-associated deficits in an Alzheimer’s disease model by restoring the BDNF signaling

Project description:Over the past decade, genetic evidence has demonstrated that microglial dysregulation is likely to play a central role in the development of Alzheimer's disease (AD). As resident immune cells in the brain, microglia become dystrophic and senescent during the chronic progression of AD. To explore whether replenishing the brain with new microglia is beneficial to AD, we employed a CSF1R inhibitor PLX3397 to deplete microglia and induce repopulation after the inhibitor withdrawal in 5xFAD transgenic mice. We observed that microglial repopulation ameliorates AD-associated cognitive deficits, accompanied by elevation of synaptic proteins and hippocampal long-term potentiation (LTP). In addition, microglial morphology is restored after microglial self-renewal, and amyloid pathology is reduced with long-term repopulation but not short-term. Transcriptome analysis showed that repopulating microglia in 5xFAD mice recovers a gene expression profile that is highly similar to microglia from WT mice. Notably, the neurotrophic signaling pathway and hippocampal neurogenesis dysregulated in the AD brain are restored after microglial replenishment. At last, we confirmed that microglial repopulation rescues brain-derived neurotrophic factor (BDNF) expression to contribute to synaptic plasticity. Together, we conclude that microglial self-renewal benefits AD brain by restoring the BDNF neurotrophic signaling pathway. Thus, the proper replenishment of microglia may be an effective and novel therapeutic strategy for ameliorating cognition impairment in AD.

2023-07-24 | GSE223156 | GEO

Aberrant L-Fucose accumulation and increased core fucosylation are specific metabolic liabilities in mesenchymal glioblastoma

Project description:Dysregulated metabolism in glioblastoma (GBM), the deadliest brain tumor of adults, offers an opportunity to deploy metabolic interventions as precise therapeutic strategies. To identify the molecular drivers and the modalities by which different molecular subgroups of GBM exploit metabolic rewiring to sustain tumor progression, we interrogated the transcriptome, the metabolome and the glycoproteome of human subgroup-specific GBM stem cells (GSCs). Here we report that L-Fucose abundance and core fucosylation activation are more highly enhanced in mesenchymal (MES) than in proneural (PN) GSCs; this pattern is retained in subgroup-specific xenografts and, most significantly, retrieved in subgroup-affiliated human patients’ samples. Genetic and pharmacological inhibition of core fucosylation in MES GBM preclinical models results in significant reduction in tumor burden. LC/MS-based glycoproteomic screening indicates that most MES-restricted core fucosylated proteins are involved in therapeutically relevant GBM pathological processes, such as extracellular matrix interaction, cell adhesion and integrin-mediated signaling. Notably, selective L-Fucose accumulation in MES GBMs is demonstrated by pre-clinical minimally-invasive positron emission tomography (PET), implying this metabolite as a potential subgroup-restricted biomarker. Overall, these findings indicate that L-Fucose pathway activation in MES GBM offers subgroup-specific, GSC-restricted dependencies to be exploited as diagnostic markers and actionable therapeutic targets.

2022-11-08 | GSE202200 | GEO

KChIP3 promotes Alzheimer´s disease by impairing long-term potentiation and memory

Project description:Alzheimer's disease (AD) is a multifactorial disorder with serious social, health, and economic implications, affecting over 30 million individuals worldwide, and this number may triple by the year 2050. To date, there are no accurate biomarkers for early diagnosis nor effective treatments to delay the progression of the disease. AD is characterized by extracellular senile plaques, intracellular neurofibrillary tangles, microglia activation, synapse loss, and inflammation leading to neuronal degeneration and cognitive decline. However, the molecular mechanisms underlying this inflammatory process are not fully understood. In this sense, increased levels of KChIP3 in the brains of postmortem AD patients and AD mouse models have been reported. Here, we propose that KChIP3 participates in AD development by maintaining an inflammatory state that negatively impacts cognitive functions. To test this hypothesis, we knock out the expression of KChIP3 in the AD mouse model 5XFAD (5XFAD/KChIP3-/-). We discovered that the absence of KChIP3 reduces the learning and memory capacity of the 5XFAD mice, reduces hippocampal inflammatory molecules and beta-amyloid plaque deposition, and rescued the reduced number and length of hippocampal dendrites and LTP in the 5XFAD mice. Transcriptomic and quantitative proteomic approaches revealed decreased levels of inflammatory mediators and enrichment of molecules related to synaptic transmission, LTP, and learning and memory in the hippocampus of 5XFAD/KChIP3-/-. Our data point out KChIP3 as a therapeutic target to restore the central nervous system's immune suppressive status, favoring the protective effect of the innate immune response in Alzheimer´s disease.

2025-06-30 | PXD054699 | Pride

L-Fucose is a candidate monosaccharide neuromodulator and mitigates Alzheimer’s synaptic deficits II

Project description:L-Fucose is a candidate monosaccharide neuromodulator and mitigates Alzheimer’s synaptic deficits II

| PRJNA1254721 | ENA

Pyrazole-derived TRPC3 antagonist ameliorates synaptic dysfunctions and memory deficits in Alzheimer’s disease models

Project description:Among the canonical transient receptor potential (TRPC) channels, TRPC3 expression is uniquely upregulated in brains with Alzheimer’s disease (AD) based on our recent studies. Herein, we used JW-65, a selective inhibitor for TRPC3 over TRPC6, to investigate the potentially distinct role of TRPC3 in AD. JW-65 treatment completely restored impaired synaptic plasticity and learning memory in acute and chronic experimental AD models. JW-65 treatment of symptomatic 5XFAD transgenic mice reversed the impaired LTP, correlating with their largely corrected synaptic gene expression based on hippocampal RNA-seq data analysis. JW-65 also provided synaptic protection in primary rat hippocampal neurons against soluble β-amyloid oligomers (AβOs), primarily via restoring the AβOs-impaired Ca2+/calmodulin-mediated signaling pathways. JW-65 treatment also significantly prevented  Ca2+ overload induced by AβOs. These findings suggest that aberrantly upregulated TRPC3, as a novel non-selective ion channel, significantly contributes to Ca2+ dyshomeostasis in AD. Our work identifies TRPC3 as a potential therapeutic target for treating synaptic dysfunction of AD.

2025-07-17 | GSE253510 | GEO

Different effects of constitutive and induced microbiota modulation on microglia in a mouse model of Alzheimer’s disease

Project description:It was recently revealed that gut microbiota promote amyloid-beta (Aβ) burden in mouse models of Alzheimer’s disease (AD). However, the underlying mechanisms when using either germ-free (GF) housing conditions or treatments with antibiotics (ABX) remained unknown. In this study, we show that GF and ABX-treated 5x familial AD (5xFAD) mice developed attenuated hippocampal Aβ pathology and associated neuronal loss, and thereby delayed disease-related memory deficits. While Ab production remained unaffected in both GF and ABX-treated 5xFAD mice, we noticed in GF 5xFAD mice enhanced microglial Aβ uptake at early stages of the disease compared to ABX-treated 5xFAD mice. Furthermore, RNA-sequencing of hippocampal microglia from SPF, GF and ABX-treated 5xFAD mice revealed distinct microbiota-dependent gene expression profiles associated with phagocytosis and altered microglial activation states. Taken together, we observed that constitutive or induced microbiota modulation in 5xFAD mice differentially controls microglial Aβ clearance mechanisms preventing neurodegeneration and cognitive deficits.

2020-07-15 | GSE154428 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data