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Proceedings of the National Academy of... Nov 2021Inflammation drives the pathology of many neurological diseases. d-mannose has been found to exert an antiinflammatory effect in peripheral diseases, but its effects on...
Inflammation drives the pathology of many neurological diseases. d-mannose has been found to exert an antiinflammatory effect in peripheral diseases, but its effects on neuroinflammation and inflammatory cells in the central nervous system have not been studied. We aimed to determine the effects of d-mannose on key macrophage/microglial functions-oxidative stress and phagocytosis. In murine experimental autoimmune encephalomyelitis (EAE), we found d-mannose improved EAE symptoms compared to phosphate-buffered saline (PBS)-control mice, while other monosaccharides did not. Multiagent molecular MRI performed to assess oxidative stress (targeting myeloperoxidase [MPO] using MPO-bis-5-hydroxytryptamide diethylenetriaminepentaacetate gadolinium [Gd]) and phagocytosis (using cross-linked iron oxide [CLIO] nanoparticles) in vivo revealed that d-mannose-treated mice had smaller total MPO-Gd areas than those of PBS-control mice, consistent with decreased MPO-mediated oxidative stress. Interestingly, d-mannose-treated mice exhibited markedly smaller CLIO areas and much less T2 shortening effect in the CLIO lesions compared to PBS-control mice, revealing that d-mannose partially blocked phagocytosis. In vitro experiments with different monosaccharides further confirmed that only d-mannose treatment blocked macrophage phagocytosis in a dose-dependent manner. As phagocytosis of myelin debris has been known to increase inflammation, decreasing phagocytosis could result in decreased activation of proinflammatory macrophages. Indeed, compared to PBS-control EAE mice, d-mannose-treated EAE mice exhibited significantly fewer infiltrating macrophages/activated microglia, among which proinflammatory macrophages/microglia were greatly reduced while antiinflammatory macrophages/microglia increased. By uncovering that d-mannose diminishes the proinflammatory response and boosts the antiinflammatory response, our findings suggest that d-mannose, an over-the-counter supplement with a high safety profile, may be a low-cost treatment option for neuroinflammatory diseases such as multiple sclerosis.
Topics: Animals; Drug Evaluation, Preclinical; Encephalomyelitis, Autoimmune, Experimental; Female; Mannose; Mice, Inbred C57BL; Molecular Imaging; Oxidative Stress; Phagocytosis; Mice
PubMed: 34702739
DOI: 10.1073/pnas.2107663118 -
Immunology Today Nov 1996
Review
Topics: Carrier Proteins; Humans; Immunity, Innate; Lectins; Mannose; Mannose-Binding Lectins
PubMed: 8961631
DOI: 10.1016/0167-5699(96)10062-1 -
Nihon Rinsho. Japanese Journal of... Feb 1995
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Nihon Rinsho. Japanese Journal of... Aug 1999
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Nihon Rinsho. Japanese Journal of... Nov 2004
Topics: Humans; Mannose
PubMed: 15628499
DOI: No ID Found -
Urologie (Heidelberg, Germany) Aug 2023
Topics: Humans; Mannose; Urinary Tract Infections; Cystitis
PubMed: 37380784
DOI: 10.1007/s00120-023-02136-y -
Chemistry, An Asian Journal Sep 2022Leishmaniasis, caused by the intramacrophage protozoan parasite Leishmania donovani, is a life-threatening yet neglected vector-borne disease. Few medications for the...
Leishmaniasis, caused by the intramacrophage protozoan parasite Leishmania donovani, is a life-threatening yet neglected vector-borne disease. Few medications for the treatment of this disease are available. However, targeted delivery of drugs to macrophages remains a significant concern. Macrophages are equipped with many receptors, and therefore putting suitable ligands in the macrophage targeting drug delivery vehicle gained a lot of attention. One such receptor is the mannose receptor, abundantly expressed by macrophages. To treat this deadly disease, in this study, a mannose containing composite hydrogel is prepared by combining a self-aggregating short peptide (Nap-FFGE-NH , Pep-A) and a mannose containing non-aggregating peptide (Nap-FF-mannosyl, Pep-B). The self-aggregation of the composite hydrogel is evaluated using various spectroscopic and microscopic techniques. Intermolecular hydrogen bonding and π-π stacking lead to an antiparallel β-sheet like arrangement of the peptides. Notably, the composite hydrogel showed shear-thinning and syneresis properties. Moreover, the composite hydrogel was found to be stable in cell-culture media, biodegradable and non-toxic to the macrophages. Both control and infected macrophages showed effective cell growth and proliferation when subjected to the composite 2D and 3D hydrogel matrix. When treated with Amphotericin B loaded composite hydrogel, the drug was effectively delivered to kill the parasite in the infected macrophages. Almost 3.5 fold decrease in the parasite burden was recorded when infected cells were treated with drug-loaded composite hydrogel. The injectability, biodegradability, non-cytotoxicity, and efficient drug delivery properties of the mannose-functionalized hydrogel make it a suitable candidate for the treatment of Leishmaniasis.
Topics: Humans; Hydrogels; Leishmaniasis; Leishmaniasis, Visceral; Mannose; Peptides
PubMed: 35871609
DOI: 10.1002/asia.202200550 -
Orphanet Journal of Rare Diseases Oct 2019PMM2-CDG (Phosphomannomutase 2 - Congenital disorder of glycosylation-Ia; CDG-Ia) is the most common glycosylation defect, often presenting as a severe multisystem...
BACKGROUND
PMM2-CDG (Phosphomannomutase 2 - Congenital disorder of glycosylation-Ia; CDG-Ia) is the most common glycosylation defect, often presenting as a severe multisystem disorder that can be fatal within the first years of life. While mannose treatment has been shown to correct glycosylation in vitro and in vivo in mice, no convincing effects have been observed in short-term treatment trials in single patients so far.
RESULTS
We report on a boy with a severe PMM2-CDG who received a continuous intravenous mannose infusion over a period of 5 months during the first year of life in a dose of 0.8 g/kg/day. N-glycosylation of serum glycoproteins and mannose concentrations in serum were studied regularly. Unfortunately, no biochemical or clinical improvement was observed, and the therapy was terminated at age 9 months.
CONCLUSION
Postnatal intravenous D-mannose treatment seems to be ineffective in PMM2-CDG.
Topics: Congenital Disorders of Glycosylation; Drug Administration Schedule; Fatal Outcome; Humans; Infant; Male; Mannose; Phosphotransferases (Phosphomutases); Transferrins
PubMed: 31640729
DOI: 10.1186/s13023-019-1213-3 -
Bioanalysis Dec 2018Urinary tract infections (UTIs) are increasingly antibiotic resistant, and alternate or adjunct therapies are urgently needed. Several studies suggest that D-mannose...
AIM
Urinary tract infections (UTIs) are increasingly antibiotic resistant, and alternate or adjunct therapies are urgently needed. Several studies suggest that D-mannose ingestion and a hypothesized increase in urinary D-mannose reduce UTI frequency. Our goal was to develop a reliable assay for urinary D-mannose, which is needed to assess the effects of supplemental D-mannose on urinary D-mannose and UTIs.
RESULTS
We developed an enzymatic assay for D-mannose in urine. Hexoses in urine were phosphorylated, sequentially isomerized and oxidized, and the increases in reduced NADPH were measured in a spectrophotometer. Urinary mannose from ten volunteers was well above the detection limit and ranged from 8 to 700 μM.
CONCLUSION
A rapid, reliable, and sensitive assay was developed, readily detected urinary D-mannose, and is adaptable to high-throughput analysis. If urinary D-mannose is shown to correlate with susceptibility to UTIs, then the assay could assess susceptibility to UTIs and direct mannose therapy.
Topics: Enzyme Assays; Female; Glucosephosphate Dehydrogenase; Hexokinase; High-Throughput Screening Assays; Humans; Mannose; Saccharomyces cerevisiae
PubMed: 30412675
DOI: 10.4155/bio-2018-0121 -
Angewandte Chemie (International Ed. in... Jul 2018O-Mannose glycans account up to 30 % of total O-glycans in the brain. Previous synthesis and functional studies have only focused on the core M3 O-mannose glycans of...
O-Mannose glycans account up to 30 % of total O-glycans in the brain. Previous synthesis and functional studies have only focused on the core M3 O-mannose glycans of α-dystroglycan, which are a causative factor for various muscular diseases. In this study, a highly efficient chemoenzymatic strategy was developed that enabled the first collective synthesis of 63 core M1 and core M2 O-mannose glycans. This chemoenzymatic strategy features the gram-scale chemical synthesis of five judiciously designed core structures, and the diversity-oriented modification of the core structures with three enzyme modules to provide 58 complex O-mannose glycans in a linear sequence that does not exceed four steps. The binding profiles of synthetic O-mannose glycans with a panel of lectins, antibodies, and brain proteins were also explored by using a printed O-mannose glycan array.
Topics: Animals; Biocatalysis; Chemistry Techniques, Synthetic; Dystroglycans; Glycosylation; Glycosyltransferases; Humans; Mannose; Polysaccharides
PubMed: 29802667
DOI: 10.1002/anie.201804373