| 2023 |
Crystal/cryo-EM structure of murine NEU1 was determined, revealing that the enzyme oligomerizes through two self-association interfaces, displays a wide substrate-binding cavity, and contains a catalytic loop that adopts an inactive conformation. A mechanism of activation was proposed involving a conformational change in this loop upon binding to its protective protein PPCA/cathepsin A. |
Structure determination (3D structural analysis), biochemical characterization |
Science advances |
High |
37205763
|
| 2009 |
NEU1 (and not NEU2, NEU3, or NEU4) forms a complex with TLR-2, -3, and -4 on the cell surface of naïve macrophages. Ligand binding to TLR4 (LPS) induces NEU1 sialidase activity, which hydrolyzes alpha-2,3-sialyl residues on TLR4, removing steric hindrance to TLR4 dimerization, MyD88/TLR4 complex formation, and subsequent NFκB activation. This was confirmed using primary Neu1-deficient macrophages (which fail to respond), catalytically inactive trans-sialidase mutant (which cannot substitute), and the neuraminidase inhibitor Tamiflu. |
Co-immunoprecipitation, live-cell sialidase assay, pharmacological inhibition (Tamiflu/DANA/zanamivir), lectin blocking, primary Neu1-deficient macrophages, HEK293 reconstitution with TLR4/MD2 |
Cellular signalling |
High |
19430901 19796680
|
| 2009 |
NEU1 forms a stable heterodimer with protective protein/cathepsin A (PPCA). PPCA acts as a molecular chaperone that prevents premature self-oligomerization of NEU1 by competing for a NEU1 self-association interface. In the absence of PPCA (as in galactosialidosis), NEU1 self-associates into chain-like oligomers. PPCA binding reverses NEU1 self-oligomerization by disassembling NEU1 oligomers into a PPCA-NEU1 heterodimer. |
Hydrodynamic analysis (analytical ultracentrifugation), binding site mapping, structural modeling, biochemical reconstitution |
The Journal of biological chemistry |
High |
19666471
|
| 2006 |
During monocyte-to-macrophage differentiation, NEU1 relocalizes from lysosomes to the cell surface via LAMP-2-negative, MHC class II-positive vesicles that merge with the plasma membrane. Cathepsin A, which forms a complex with and activates NEU1 in lysosomes, is co-sorted to the plasma membrane. siRNA suppression of NEU1 or anti-NEU1 antibodies reduced macrophage phagocytosis of bacteria and cytokine production. |
Immunofluorescence, subcellular fractionation, siRNA knockdown, anti-Neu1 antibody blocking, flow cytometry |
The Journal of biological chemistry |
High |
16835219
|
| 2007 |
The catalytic sialidase activity of the NEU1 subunit of the elastin receptor complex (ERC) is responsible for ERK1/2 activation and pro-MMP-1 production induced by elastin peptide binding. A catalytically inactive NEU1 mutant and siRNA-mediated NEU1 knockdown both abolished elastin peptide-induced ERK1/2 activation and pro-MMP-1 production in skin fibroblasts. N-acetyl neuraminic acid (sialic acid) could reproduce the elastin peptide effects. |
Pharmacological inhibition, catalytically inactive NEU1 mutant, siRNA knockdown, ERK1/2 activation assay, pro-MMP-1 production assay |
The Journal of biological chemistry |
High |
17327233
|
| 2011 |
On the surface of naive macrophage cells, NEU1 forms a complex with MMP-9, both of which are constitutively bound to TLR4. LPS binding to TLR4 activates Gαi GPCR signaling, which activates MMP-9, which in turn activates NEU1 sialidase. NEU1-mediated TLR4 desialylation and NFκB activation are blocked by specific MMP-9 inhibition, Gαi-pathway inhibition, MMP-9 shRNA/siRNA knockdown, and are absent in MMP-9 knockout macrophages. |
Co-immunoprecipitation, siRNA/shRNA knockdown, MMP-9 KO macrophages, lentiviral transduction, pharmacological inhibition, live-cell sialidase assay |
The Journal of biological chemistry |
High |
21873432
|
| 2010 |
Neu1 and MMP-9 form a complex bound to TrkA on the surface of naive neurons and TrkA-expressing cells. NGF binding to TrkA activates GPCR Gαi signaling → MMP-9 activation → Neu1 sialidase activation. Tamiflu (oseltamivir phosphate) blocks NGF-induced Neu1 activity and subsequent Trk receptor activation and neurite outgrowth in TrkA-PC12 cells. |
Co-immunoprecipitation, live-cell sialidase assay, pharmacological inhibition (Tamiflu), TrkA-PC12 cell lines, primary neurons |
Cellular signalling |
Medium |
20347965
|
| 2009 |
NEU1 overexpression in human colon cancer HT-29 cells desialylates integrin beta4 (removing alpha-2,3 and O-glycan sialic acids), reduces integrin beta4 phosphorylation, attenuates focal adhesion kinase (FAK) and Erk1/2 signaling, and downregulates MMP-7, leading to suppressed cell migration, invasion, adhesion, and in vivo liver metastasis. |
NEU1 overexpression and siRNA knockdown, lectin blotting of integrin beta4 immunoprecipitates, immunofluorescence, biotinylation assay, O-glycosylation inhibitor (GalNAc-α-O-benzyl), in vivo transsplenic injection model |
Oncogene |
High |
19151752
|
| 2012 |
In human airway epithelial cells, NEU1 sialidase directly associates with EGFR and MUC1 and accounts for >70% of cellular sialidase activity. NEU1 overexpression diminishes EGF-stimulated EGFR Tyr-1068 autophosphorylation, while NEU1 depletion increases EGFR activation. NEU1 also desialylates MUC1, enhancing MUC1-dependent Pseudomonas aeruginosa adhesion and flagellin-stimulated ERK1/2 activation. |
Co-immunoprecipitation, NEU1 overexpression/siRNA, lectin blotting (MAL-2/PNA), EGFR phosphorylation assay, bacterial adhesion assay |
The Journal of biological chemistry |
High |
22247545
|
| 2013 |
NEU1 deficiency in mice leads to accumulation and amyloidogenic processing of an oversialylated amyloid precursor protein (APP) in lysosomes, followed by excessive lysosomal exocytosis that releases Aβ peptides extracellularly. Cerebral injection of NEU1 into an established AD mouse model substantially reduces β-amyloid plaques. |
NEU1-deficient mouse model, APP processing analysis, lysosomal fractionation, Aβ ELISA, cerebral NEU1 injection rescue experiment |
Nature communications |
High |
24225533
|
| 2014 |
TLR4 activation triggers NEU1 translocation to the cell surface, where NEU1 disrupts the inhibitory TLR4:Siglec-E interaction by desialylating TLR4. Sialidase inhibitor Neu5Gc2en prevents TLR4 ligand-induced disruption of TLR4:Siglec-E/F interactions. Absence of NEU1 in hematopoietic cells protects mice against endotoxemia, demonstrating that NEU1-mediated de-repression of TLR4 from Siglec inhibition is a positive feedback mechanism for TLR activation during infection. |
Cell surface translocation assay, sialidase inhibitor treatment (Neu5Gc2en), Neu1-conditional hematopoietic KO mice, TLR4:Siglec interaction co-IP/pulldown, endotoxemia mouse model |
eLife |
High |
25187624
|
| 2014 |
Catalytically active NEU1 inhibits in vitro angiogenesis (capillary-like tube formation) through desialylation of its substrate CD31 in postconfluent human pulmonary microvascular endothelial cells. A catalytically dead NEU1 mutant (G68V) did not inhibit tube formation. Prior CD31 silencing or use of CD31-null ECs abrogated NEU1's inhibitory effect, and forced CD31 sialylation (via sialyltransferase ST6GAL-I overexpression) counteracted NEU1-mediated inhibition. |
NEU1 overexpression with catalytic mutant control (G68V), siRNA knockdown of NEU1/CD31, CD31-null ECs, lectin blotting (SNA/PNA), Matrigel tube formation assay, wounding assay |
The Journal of biological chemistry |
High |
24550400
|
| 1998 |
A single amino acid substitution L209I in the Neu1 protein is responsible for the partial neuraminidase deficiency in SM/J mice. The mutant enzyme is correctly localized to lysosomes and retains the ability to associate with its activating protein PPCA, but the reduced activity is caused by altered substrate affinity rather than changed substrate specificity or turnover rate. |
Genetic analysis, sequencing, site-directed mutagenesis, enzyme activity assays, lysosomal fractionation, PPCA binding assay |
Human molecular genetics |
High |
9425240
|
| 2004 |
Five novel NEU1 mutations (R225P, A298V, M1?, R341G, W23X) in type II sialidosis patients abolish enzymatic sialidase activity when expressed via recombinant adenovirus. The R341G mutation perturbs substrate binding, while A298V and R225P impair enzyme folding, as determined by activity assay and immunofluorescence localization analysis. |
Adenoviral expression of mutant sialidases in primary cell cultures, sialidase activity assay, intracellular localization (immunofluorescence) |
Human mutation |
High |
14695530
|
| 2012 |
NEU1 is the dominant sialidase in human lung microvascular endothelial cells (expressed ~2700-fold more than NEU2/3/4), localizes to both plasma membrane and perinuclear regions, and restrains endothelial cell migration. NEU1 overexpression reduced EC migration into wounds by >40%, whereas NEU3 overexpression did not. siRNA knockdown of NEU1 decreased >65% of total sialidase activity for 4-MU-NANA substrate. |
Real-time RT-PCR, Western blot, confocal microscopy/flow cytometry (localization), siRNA knockdown, wound-healing migration assay, sialidase activity assay |
The Journal of biological chemistry |
High |
22403397
|
| 2010 |
Neu1 sialidase is required for hyaluronic acid receptor function of CD44 on CD4+ T cells. Antigen stimulation induces Neu1 expression on splenic CD4+ T cells from asthmatic mice, and increased Neu1 activity removes inhibitory sialic acid residues from CD44 to enable HA binding and T helper type 2-mediated airway inflammation. Sialidase inhibitor treatment suppressed HA binding, and Neu1-deficient SM/J mice showed reduced Th2 airway inflammation and airway hyperresponsiveness. |
Flow cytometry (HA-binding), real-time RT-PCR, pharmacological sialidase inhibition, Neu1-deficient SM/J mouse model, cytokine analysis, airway hyperresponsiveness measurement |
Clinical and experimental immunology |
Medium |
20491786
|
| 2013 |
NEU1 and MMP-9 form a tripartite complex with neuromedin B GPCR, TLR-7, and TLR-9. Ligand-induced activation of endosomal TLR-7 and TLR-9 requires this NMBR-MMP9-Neu1 cross-talk signaling platform. siRNA silencing of Neu1, MMP-9, or NMBR each significantly reduced nucleic acid-induced NFκB activation and TNFα/MCP-1 cytokine responses. |
siRNA knockdown, complex formation (immunoprecipitation), NFκB reporter assay, SEAP reporter, pharmacological inhibitors (Tamiflu, MMP-9 inhibitor, BIM23127, BIM-46174) |
Cellular signalling |
Medium |
23827939
|
| 2012 |
GPCR agonists (bombesin, bradykinin, LPA, cholesterol, angiotensin-1 and -2) induce Neu1 sialidase activity in macrophages via a neuromedin B receptor (NMBR)-MMP9 signaling platform, transactivating TLR receptors and inducing NFκB activation. Bombesin receptor (NMBR) forms a complex with TLR4 and MMP9. MMP9 siRNA knockdown or MMP9 absence abolishes this GPCR-induced Neu1 activity. |
Live-cell sialidase assay, siRNA knockdown, co-immunoprecipitation, NFκB-SEAP reporter, pharmacological inhibitors, Neu1-deficient primary macrophages as negative control |
Cellular signalling |
Medium |
22759791
|
| 2013 |
Elastin-derived peptides (EDP) binding to the elastin receptor complex (ERC, which contains NEU1) activate monocyte migration and ROS production through a neuraminidase activity-dependent PI3Kγ signaling pathway. The absence of the cathepsin A-NEU1 complex in hematopoietic cells abolished atherosclerotic plaque progression in LDLR-/- mice. In vitro, PI3Kγ was required for EDP-induced monocyte migration and this was dependent upon neuraminidase activity. |
In vivo atherosclerosis mouse models, PI3Kγ KO bone marrow chimeras, cathepsin A-NEU1 complex-deficient hematopoietic cells, neuraminidase activity inhibition, monocyte migration assay, ROS production assay |
Cardiovascular research |
Medium |
24357053
|
| 2015 |
NEU1-driven MUC1 ectodomain desialylation increases binding affinity of P. aeruginosa flagellin to MUC1, promotes bacterial adhesion and invasion, and triggers MUC1-ED shedding. The shed desialylated MUC1-ED functions as a hyperadhesive decoy receptor that competitively blocks bacterial adhesion. NEU1 association with MUC1 increases upon flagellin stimulation, and NEU1 co-associates with MUC1's chaperone PPCA in this context. |
Scatchard binding analysis, NEU1/MUC1 co-immunoprecipitation, lectin blotting, NEU1 overexpression/siRNA, bacterial adhesion/invasion assay, ex vivo BAL fluid analysis |
The Journal of biological chemistry |
High |
25963144
|
| 2021 |
NEU1 directly associates with the MUC1 cytoplasmic domain (CD) at its juxtamembranous 36 amino acid region, independently of NEU1 catalytic activity and independently of PPCA chaperone. This NEU1-MUC1-CD interaction does not require NEU1 enzymatic activity for MUC1-ED desialylation. However, both wild-type NEU1 and the catalytically dead NEU1-G68V mutant inhibit PI3K binding to MUC1-CD and reduce downstream Akt phosphorylation, indicating NEU1 inhibits PI3K-Akt signaling through its scaffold function independent of catalytic activity. |
Reciprocal co-immunoprecipitation, in vitro binding assays (GST pull-down with deletion mutants), cell-free binding assay with purified proteins, catalytic dead mutant (G68V), NEU1-selective inhibitor C9-BA-DANA |
The Journal of biological chemistry |
High |
34688655
|
| 2017 |
As human pulmonary microvascular endothelial cells (HPMECs) achieve confluence, Src family kinases (SFKs) are activated and phosphorylate p120 catenin. Tyrosine-phosphorylated p120 catenin functions as an adaptor molecule that physically couples NEU1 to CD31, enabling NEU1-mediated CD31 desialylation. SFK inhibition blocks both p120ctn phosphorylation and NEU1-CD31 association. Direct protein-protein interactions between NEU1, CD31, and p120ctn were demonstrated in a cell-free system with purified recombinant proteins. |
Co-immunoprecipitation, siRNA knockdown of individual SFKs/CD31/p120ctn, SFK pharmacological inhibitors (PP2, SU6656), cell-free binding assay with purified recombinant proteins, pull-down assays |
Cellular signalling |
High |
28343945
|
| 2018 |
Membrane NEU1 interacts with CD36 (class B scavenger receptor) in human macrophages. Elastin-derived peptides (EDP) binding to the elastin receptor complex desialylate CD36 via NEU1. EDP-induced desialylation of CD36 increases uptake of oxidized LDL by macrophages, an effect blocked by both V14 peptide (blocking EDP-ERC interaction) and the sialidase inhibitor DANA. |
Proteomic purification (LC-MS/MS), co-immunoprecipitation validation, sialidase activity assay, oxidized LDL uptake assay, pharmacological inhibition (V14 peptide, DANA) |
Cellular and molecular life sciences |
Medium |
30498996
|
| 2021 |
In L. donovani-infected macrophages, Neu1 translocation to the plasma membrane is impaired due to reduced tyrosine-phosphorylation of Neu1 and diminished Neu1-cathepsin A association. Reduced membrane-bound Neu1 results in hypersialylated TLR4 (enhanced alpha-2,3-linked sialic acids), reduced Neu1-TLR4 association, impaired MyD88 recruitment, and suppressed downstream MAP kinase/NFκB signaling. NEU1 overexpression rescued TLR4 desialylation, MyD88 association, and cytokine production, reducing parasite burden. |
Immunoprecipitation, phosphorylation analysis, NEU1 overexpression, NEU1 silencing, flow cytometry, confocal microscopy, ELISA cytokine assay |
Frontiers in immunology |
Medium |
33763070
|
| 2005 |
Lysosomal sialidase (Neu1) activity is induced ~6-fold in the first 24 h of C2C12 myoblast differentiation, driven by MyoD transcriptional activation through a mechanism dependent on MyoD's chromatin remodeling domain. Inappropriate Neu1 overexpression 48 h after differentiation onset downregulates myogenin and myosin heavy chain expression and halts the myogenic differentiation cascade. |
C2C12 myoblast differentiation, sialidase activity assay, MyoD overexpression/reporter assay, Neu1 overexpression, Western blot (myogenin/MHC) |
Experimental cell research |
Medium |
16216242
|
| 2022 |
Activated microglia release Neu1 into culture medium by lysosomal exocytosis (blocked by lysosomal exocytosis inhibitors). Released/extracellular Neu1 and Neu1 overexpression increase microglial phagocytosis, while Neu1 knockdown decreases phagocytosis. Microglial activation desialylates phagocytic receptors Trem2 and MerTK via Neu1, increasing Trem2 ligand (galectin-3) binding. Conditioned medium from activated microglia containing Neu1 desialylates neurons and sensitizes them to glutamate-induced death. |
Neu1 knockdown, exocytosis inhibitor treatment, Neu1 overexpression, phagocytosis assay, co-immunoprecipitation of Trem2/MerTK, galectin-3 binding assay, neuronal desialylation and toxicity assay |
Frontiers in cellular neuroscience |
Medium |
35693885
|
| 2017 |
NEU1 interacts with perilipin 1 (Plin1) on lipid droplets under basal conditions in 3T3-L1 adipocytes, as shown by co-immunoprecipitation and co-localization. Neu1 knockdown increases glycerol release (lipolysis), Plin1 phosphorylation, and Plin1-HSL interaction upon β-adrenergic stimulation, indicating that NEU1 inhibits lipolysis by interacting with Plin1 on lipid droplets. |
siRNA knockdown, co-immunoprecipitation, immunofluorescent co-localization, glycerol concentration measurement, Plin1 phosphorylation analysis, Plin1-HSL interaction assay |
Genes to cells |
Medium |
28429532
|
| 2022 |
Cardiomyocyte-specific NEU1 deficiency in mice post-myocardial infarction reduces cardiac dysfunction, hypertrophy, fibrosis, mitochondrial dysfunction, and oxidative stress. The mechanism involves NEU1 deficiency increasing SIRT1 and PGC-1α expression; SIRT1 activity inhibition or PGC-1α knockout abolished the beneficial effects of NEU1 deficiency, placing NEU1 upstream of the SIRT1/PGC-1α axis in post-MI cardiac metabolism. |
Cardiomyocyte-specific NEU1 KO mice (MI model), SIRT1 activity inhibitor, PGC-1α KO mice, echocardiography, Western blot, mitochondrial metabolic assays, oxidative stress assays |
Frontiers in cardiovascular medicine |
Medium |
35548408
|
| 2023 |
NEU1 regulates coronavirus replication by controlling sialylation on the coronavirus nucleocapsid protein. Coronavirus nucleocapsid proteins from COVID-19 patients and HCoV-OC43-infected cells are heavily sialylated, and this sialylation controls RNA-binding activity and viral replication. NEU1 overexpression increased HCoV-OC43 replication, while NEU1 knockdown reduced it. A NEU1 inhibitor (Neu5Ac2en-OAcOMe) dramatically reduced HCoV-OC43 and SARS-CoV-2 replication in vitro and rescued mice from HCoV-OC43 infection-induced death. |
NEU1 overexpression and knockdown, NEU1 inhibitor treatment, nucleocapsid protein sialylation analysis, RNA-binding assay, in vivo mouse infection model, in vitro SARS-CoV-2 replication assay |
iScience |
Medium |
36714013
|
| 2021 |
NEU1 associates with and desialylates CD31 only when CD31 ectodomains are homophilically engaged in postconfluent endothelial cells. Prior NEU1 silencing completely protected against CD31 desialylation in postconfluent cells. NEU1 sialidase activity is required for inhibiting tube formation, while catalytically dead NEU1-G68V had no effect. |
siRNA knockdown, adenoviral overexpression of WT and catalytic dead mutant G68V, lectin blotting (SNA/PNA), tube formation assay, wound migration assay |
The Journal of biological chemistry |
Medium |
24550400
|
| 2009 |
A regulatory mutation (-519G→A) in the Neu1 promoter generates a consensus binding site for Nkx3 family repressors. Recombinant Nkx3.2 binds strongly to and preferentially represses the mutant promoter. This tissue-specific epigenetic mechanism causes reduced Neu1 expression in SM/J mice, contributing to impaired immune response and altered leukocyte adhesion/rolling. |
Reporter assays, recombinant Nkx3.2 binding and repression assays, intravital hepatic microcirculation imaging, SM/J mouse model |
Molecular genetics and metabolism |
Medium |
19217813
|
| 2022 |
NEU1 haploinsufficiency drives a model of pleomorphic rhabdomyosarcoma through increased lysosomal exocytosis downstream of reduced NEU1. This is evidenced by redistribution of LAMP1 to the plasma membrane of tumor and stromal cells, establishing NEU1's negative regulation of lysosomal exocytosis as a tumor-suppressor mechanism in muscle. |
NEU1 haploinsufficient mouse model (Ptch1+/-/ETV7TG+/-), LAMP1 immunolocalization, single-cell analysis of exocytic cells |
Communications biology |
Medium |
36127469
|
| 2023 |
NEU1 desialylates ATG5, an autophagy protein, under hypoxic conditions. Desialylation of ATG5 by NEU1 enhances ATG5 protein stability (via altered charge effects), promotes formation of the ATG5-ATG12-ATG16L complex, and increases autophagosome formation. NEU1 was identified as a direct interacting protein of ATG5 by co-immunoprecipitation. NEU1 knockdown or inhibition reversed hypoxia-induced autophagy and inflammatory responses in macrophages. |
Co-immunoprecipitation (NEU1-ATG5 interaction), NEU1 knockdown/inhibition, ATG5 sialylation analysis, autophagosome formation assay, ATG5-ATG12-ATG16L complex analysis |
Cellular signalling |
Medium |
37844713
|
| 2021 |
NEU1 interacts with and desialylates β2 integrin in human monocytes and desialylates ICAM-1 in endothelial cells, downstream of EDP binding to the elastin receptor complex. These desialylation events are associated with increased monocyte adhesion to and transendothelial migration across endothelial cells. |
Proteomic validation, co-immunoprecipitation, sialidase activity assay, monocyte adhesion assay, transendothelial migration assay |
Cell & bioscience |
Medium |
34903296
|
| 2018 |
NEU1 exists on the surface of mouse thymocytes and CD5 is a natural substrate for this cell-surface NEU1. The activity was identified by PNA-blot analysis of anti-CD5 immunoprecipitate and inhibited by the NEU1-selective inhibitor C9-butyl-amide-DANA. |
PNA-blot of anti-CD5 immunoprecipitate, NEU1-selective inhibitor (C9-BA-DANA), SM/J (Neu1-deficient) mouse comparison, real-time PCR |
Glycobiology |
Medium |
29897583
|
| 2017 |
GPCR agonists (bombesin, bradykinin, angiotensin I and II) activate Neu1 sialidase and insulin receptor (IR) signaling independently of insulin, via a biased GPCR signaling platform involving neuromedin B receptor (NMBR)-MMP9-Neu1 cross-talk. The angiotensin II receptor (type I) forms a multimeric complex with Neu1, IRβ, and NMBR in both naïve and stimulated HTC-IR cells. |
Co-immunoprecipitation, live-cell sialidase assay, IR phosphorylation analysis, NMBR inhibitor (BIM-23127), oseltamivir phosphate (NEU1 inhibitor) |
Cellular signalling |
Medium |
29277445
|
| 2016 |
NEU1 overexpression in pulmonary fibroblasts provokes increased collagen types I and III, accelerated MMP-14 degradation, and global gene expression changes. In lung microvascular endothelial cells, NEU1 overexpression increases T cell adhesion and disrupts capillary-like tube formation. NEU1 adenoviral delivery to mice induces lymphocyte (predominantly CD8+ T cell) accumulation in bronchoalveolar lavage and lung, plus pulmonary TGF-β and collagen elevation, recapitulating key features of lung fibrosis. |
Adenoviral NEU1 gene delivery (in vitro and in vivo), collagen assay, MMP-14 analysis, wounding assay, T cell adhesion assay, tube formation assay, BAL cell counting |
American journal of physiology. Lung cellular and molecular physiology |
Medium |
26993524
|
| 2025 |
Epididymal epithelial cells secrete and transfer NEU1 onto the sperm surface, where it regulates α-2,6 sialylation to influence sperm maturation, energy metabolism, and capacitation. Inhibition of NEU1 activity markedly reduced sperm motility and fertilization capacity. NEU1 expression was lower in asthenozoospermic individuals and correlated with sperm kinematic parameters. |
Immunofluorescence, Western blot, flow cytometry, NEU1 activity inhibition, IVF assay, murine transfer model, sialylation analysis |
Cellular and molecular life sciences |
Medium |
41329355
|
| 2024 |
In the periosteum, fibroblast-derived NEU1 desialylates α2,3-linked sialic acid residues on osteoclasts, disrupting cell-cell recognition and maintaining osteoclasts in a mononuclear state, thereby maintaining low cortical bone metabolic activity. Targeted NEU1 inhibition in mouse models accelerated fracture healing by up to 30%. Identified by single-cell RNA sequencing of human periosteum combined with in vitro and in vivo NEU1 inhibition experiments. |
Single-cell RNA sequencing, NEU1 inhibition (in vitro and in vivo), osteoclast mononuclear state analysis, fracture healing mouse model, bone quality/mechanical strength assessment |
Theranostics |
Medium |
41356197
|