{"doi":"10.1101/2022.08.11.503673","title":"L-Fucose is a candidate monosaccharide neuromodulator and mitigates Alzheimer’s synaptic deficits","abstract":"Abstract We identified a novel signaling function of L-fucose, a structurally unique monosaccharide. We showed that L-fucose enhanced excitatory neurotransmission and long-term potentiation (LTP) in Schaffer-collateral-CA1 synapses. L-fucose was released by neurons in an activity- and store-dependent manner, and induced rapid signaling changes to enhance presynaptic release. Such effects required L-fucose metabolism through the salvage pathway driven by fucokinase (FUK). Thus, L-fucose could be the first described monosaccharide neuromodulator affecting 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 could be corrected by exogenous L-fucose, exemplified by rectification of LTPdeficits in 5xFAD hippocampus. Dietary L-fucose supplement, which increased cerebral free L-fucose levels and upregulated FUK to drive the salvage pathway, mitigated synaptic and behavioral deficits of 5xFAD mice. Our data reveals a therapeutic potential of oral L-fucose for AD, which is safe and easy to comply with.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":301691,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9524,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":896091,"name":"Jennyfer Tena","orcid":"0000-0001-6660-0445","position":1,"is_corresponding":false},{"id":993139,"name":"Ulises Ruiz Mendiola","orcid":"0000-0002-7429-3614","position":2,"is_corresponding":false},{"id":313621,"name":"Xi Chen","orcid":"0000-0002-3160-614X","position":3,"is_corresponding":false},{"id":235510,"name":"Carlito B. Lebrilla","orcid":"0000-0001-7190-5323","position":4,"is_corresponding":false},{"id":322717,"name":"Izumi Maezawa","orcid":"0000-0002-8666-3520","position":5,"is_corresponding":false},{"id":585338,"name":"Lee‐Way Jin","orcid":"0000-0001-9729-1032","position":6,"is_corresponding":false},{"id":322715,"name":"Jacopo Di Lucente","orcid":"0000-0001-5312-5542","position":0,"is_corresponding":true}],"reference_count":47,"raw_metadata":null,"created_at":"2026-07-19T00:32:06.309890Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}