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Gangliosides are major glycans on vertebrate nerve cells, and their metabolic disruption results in congenital disorders with marked cognitive and motor deficits. The sialyltransferase gene St3gal2 is responsible for terminal sialylation of two prominent brain gangliosides in mammals, GD1a and GT1b. In this study, we analyzed the expression of calcium-binding interneurons in primary sensory (somatic, visual, and auditory) and motor areas of the neocortex, hippocampus, and striatum of St3gal2-null mice as well as St3gal3-null and St3gal2/3-double null. Immunohistochemistry with highly specific primary antibodies for GABA, parvalbumin, calretinin, and calbindin were used for interneuron detection. St3gal2-null mice had decreased expression of all three analyzed types of calcium-binding interneurons in all analyzed regions of the neocortex. These results implicate gangliosides GD1a and GT1b in the process of interneuron migration and maturation. [ABSTRACT FROM AUTHOR]

Objective: Individual differences were observed in the clinical efficacy of Botulinum toxin A (BoNT-A) in the treatment of the primary Meige syndrome. Our study aimed to explore the potential associations between the clinical efficacy of BoNT-A in the treatment of the primary Meige syndrome and variants of SNAP25, SV2C and ST3GAL2, which are involving in the translocation of the BoNT-A in vivo. Methods: Patients with the primary Meige syndrome treated with BoNT-A were enrolled. Clinical efficacy was evaluated by the maximum improvement rate of motor symptoms and the duration of efficacy. Variants of SNAP25, SV2C and ST3GAL2 were obtained by Sanger sequencing. Another cohort diagnosed with primary cervical dystonia was also enrolled in the replication stage. Results: Among the 104 primary Meige syndrome patients, 80 patients (76.9%) had a good efficacy (the maximum improvement rate of motor symptoms ≥30%) and 24 (23. 1%) had a poor (the maximum improvement rate of motor symptoms

Gangliosides are major glycans on vertebrate nerve cells, and their metabolic disruption results in congenital disorders with marked cognitive and motor deficits. The sialyltransferase gene St3gal2 is responsible for terminal sialylation of two prominent brain gangliosides in mammals, GD1a and GT1b. In this study, we analyzed the expression of calcium-binding interneurons in primary sensory (somatic, visual, and auditory) and motor areas of the neocortex, hippocampus, and striatum of St3gal2-null mice as well as St3gal3-null and St3gal2/3-double null. Immunohistochemistry with highly specific primary antibodies for GABA, parvalbumin, calretinin, and calbindin were used for interneuron detection. St3gal2-null mice had decreased expression of all three analyzed types of calcium-binding interneurons in all analyzed regions of the neocortex. These results implicate gangliosides GD1a and GT1b in the process of interneuron migration and maturation.

In neurological diseases, the regulation of autophagy plays a crucial role in their pathology, particularly the relationship between autophagy and hepatic encephalopathy (HE) which merits detailed investigation. Glycosphingolipids are abundant and broadly functional in the nervous system and are closely associated with autophagy. However, the specific link and mechanisms between glycosphingolipids and autophagy in HE remain unclear. This study aims to explore the impact of glycosphingolipid changes on the autophagy in HE and its potential mechanisms. Utilizing lectin microarrays, we observed elevated expression levels of α2-3 sialylated glycosphingolipid in the brain tissue of HBV transgenic mice and ammonia-induced astrocyte models, suggesting that the increase in α2-3 sialylated glycosphingolipid is related to HE. Further research revealed that the increased expression of α2-3 sialylated glycosphingolipid, mediated by ST3GAL2, affects autophagy by regulating the autophagy initiation complex Vps34-Beclin-1. In summary, our research not only comprehensively reveals the changes in brain glycosphingolipid during HBV-related HE but also elucidates the interactions and regulatory mechanisms between α2-3 sialylated glycosphingolipid and autophagy. This study provides a new perspective on understanding the pathogenesis of HE and offers novel theories and targets for future research and treatment strategies. [ABSTRACT FROM AUTHOR]

Objective: Individual differences were observed in the clinical efficacy of Botulinum toxin A (BoNT-A) in the treatment of the primary Meige syndrome. Our study aimed to explore the potential associations between the clinical efficacy of BoNT-A in the treatment of the primary Meige syndrome and variants of SNAP25 , SV2C and ST3GAL2 , which are involving in the translocation of the BoNT-A in vivo., Methods: Patients with the primary Meige syndrome treated with BoNT-A were enrolled. Clinical efficacy was evaluated by the maximum improvement rate of motor symptoms and the duration of efficacy. Variants of SNAP25 , SV2C and ST3GAL2 were obtained by Sanger sequencing. Another cohort diagnosed with primary cervical dystonia was also enrolled in the replication stage., Results: Among the 104 primary Meige syndrome patients, 80 patients (76.9%) had a good efficacy (the maximum improvement rate of motor symptoms ≥30%) and 24 (23. 1%) had a poor (the maximum improvement rate of motor symptoms <30%). As to the duration of efficacy, 52 patients (50.0%) had a long duration of efficacy (≥4 months), and 52 (50.0%) had a short (<4 months). In terms of primary Meige syndrome, SNAP25 rs6104571 was found associating with the maximum improvement rate of motor symptoms (Genotype: P  = 0.02, OR = 0.26; Allele: P  = 0.013, OR = 0.29), and SV2C rs31244 was found associating with the duration of efficacy (Genotype: P  = 0.024, OR = 0.13; Allele: P  = 0.012, OR = 0.13). Besides, we also conducted the association analyses between the variants and BoNT-A-related adverse reactions. Although, there was no statistical difference between the allele of SV2C rs31244 and BoNT-A-related adverse reactions, there was a trend ( P  = 0.077, OR = 2.56). In the replication stage, we included 39 patients with primary cervical dystonia to further expanding the samples' size. Among the 39 primary cervical dystonia patients, 25 patients (64.1%) had a good efficacy (the maximum improvement rate of motor symptoms ≥50%) and 14 (35.9%) had a poor (the maximum improvement rate of motor symptoms <50%). As to the duration of efficacy, 32 patients (82.1%) had a long duration of efficacy (≥6 months), and 7 (17.9%) had a short (<6 months). Integrating primary Meige syndrome and primary cervical dystonia, SV2C rs31244 was still found associating with the duration of efficacy (Genotype: P  = 0.002, OR = 0. 23; Allele: P  = 0.001, OR = 0. 25)., Conclusion: In our study, SNAP25 rs6104571 was associated with the maximum improvement rate of motor symptoms in patients with primary Meige syndrome treated with BoNT-A, and patients carrying this variant had a lower improvement rate of motor symptoms. SV2C rs31244 was associated with duration of treatment in patients with primary Meige syndrome treated with BoNT-A and patients carrying this variant had a shorter duration of treatment. Patients with primary Meige syndrome carrying SV2C rs31244 G allele have an increase likelihood of BoNT-A-related adverse reactions. Involving 39 patients with primary cervical dystonia, the results further verify that SV2C rs31244 was associated with duration of treatment and patients carrying this variant had a shorter duration of treatment., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Spinal cord microglia contribute to nerve injury‐induced neuropathic pain. We have previously demonstrated that toll‐like receptor 2 (TLR2) signaling is critical for nerve injury‐induced activation of spinal cord microglia, but the responsible endogenous TLR2 agonist has not been identified. Here, we show that nerve injury‐induced upregulation of sialyltransferase St3gal2 in sensory neurons leads to an increase in expression of the sialylated glycosphingolipid, GT1b. GT1b ganglioside is axonally transported to the spinal cord dorsal horn and contributes to characteristics of neuropathic pain such as mechanical and thermal hypersensitivity. Spinal cord GT1b functions as an TLR2 agonist and induces proinflammatory microglia activation and central sensitization. Pharmacological inhibition of GT1b synthesis attenuates nerve injury‐induced spinal cord microglia activation and pain hypersensitivity. Thus, the St3gal2‐GT1b‐TLR2 axis may offer a novel therapeutic target for the treatment of neuropathic pain. Synopsis: Peripheral nerve injury upregulates GT1b in the injured sensory neurons, which is released in the spinal cord and functions as an endogenous agonist of microglial TLR2. Nerve injury upregulates St3gal2 and subsequent GT1b synthesis in injured DRG neurons.GT1b functions as an endogenous agonist of TLR2 to activate microglia.Antagonizing St3gal2‐GT1b‐TLR2 signaling attenuates neuropathic pain. [ABSTRACT FROM AUTHOR]

Ganglioside GT1b is well-known for its role in cytokine production and in activating epidermal growth factor receptor (EGFR)-mediated signaling pathways in cancer cells. However, there are no reports that clearly elucidate the role of GT1b in EGFR-mediated signaling pathways in porcine oocytes during the process of in vitro maturation (IVM). In this study, we investigated the role of GT1b in EGFR-mediated activation of the ERK1/2 pathway in porcine cumulus-oocyte complexes (COCs) at 44 h of IVM. Our data show that expression of the ST3GAL2 protein significantly increased in porcine COCs at 44 h irrespective of treatment with EGF. Meiotic maturation and mRNA levels of factors (HAS2, TNFAIP6, and PTX3) related to cumulus cell expansion significantly increased in COCs treated with 2 μM GT1b during IVM in the absence of EGF. They also increased in COCs treated with EGF/GT1b as compared to that in the other groups. Interestingly, protein levels of EGFR, phospho-EGFR, ERK1/2, and phospho-ERK1/2 dramatically increased in COCs treated with EGF/GT1b. Moreover, the rate of fertilization and the developmental competence of blastocyst were significantly higher in EGF/GT1b-treated COCs. Taken together, these results suggest that exogenous GT1b improves meiotic maturation and cumulus cell expansion in porcine COCs via activation of EGFR-mediated ERK1/2 signaling. [ABSTRACT FROM AUTHOR]

Ganglioside GD1a is specifically formed by the addition of sialic acid to ganglioside GM1a by ST3 β- galactoside α -2,3-sialyltransferase 2 (ST3GAL2). Above all, GD1a are known to be related with the functional regulation of several growth factor receptors, including activation and dimerization of epidermal growth factor receptor (EGFR) in tumor cells. The activity of EGF and EGFR is known to be a very important factor for meiotic and cytoplasmic maturation during in vitro maturation (IVM) of mammalian oocytes. However, the role of gangliosides GD1a for EGFR-related signaling pathways in porcine oocyte is not yet clearly understood. Here, we investigated that the effect of ST3GAL2 as synthesizing enzyme GD1a for EGFR activation and phosphorylation during meiotic maturation. To investigate the expression of ST3GAL2 according to the EGF treatment (0, 10 and 50 ng/ml), we observed the patterns of ST3GAL2 genes expression by immunofluorescence staining in denuded oocyte (DO) and cumulus cell-oocyte-complex (COC) during IVM process (22 and 44 h), respectively. Expression levels of ST3GAL2 significantly decreased (p

Mouse FBJ virus-induced osteosarcoma FBJ-S1 cells rich in GD1a are not readily metastatic, whereas FBJ-LL cells with low levels of GD1a are highly metastatic. GD1a was previously shown to suppress metastasis of mouse FBJ cells and to upregulate caveolin-1 and stromal interaction molecule 1 expression. The present study demonstrates that matrix metalloproteinase-9 (MMP-9) expression renders FBJ-LL cells invasive. MMP-9 is inversely regulated by GD1a, based upon four observations: MMP-9 mRNA content was 5 times higher in FBJ-LL cells than FBJ-S1 cells; a GD1a-re-expressing FBJ-LL cell variant produced through β1,4GalNAcT-1 cDNA transfection expressed lower levels of MMP-9; exogenous addition of GD1a to FBJ-LL cells decreased MMP-9 production in a dose- and time-dependent manner; and treatment of GD1a-rich cells with D-PDMP or siRNA targeting St3gal2 decreased GD1a expression, but augmented MMP-9 expression. This is the first report demonstrating that GD1a negatively regulates expression of MMP-9 at the transcriptional level. [ABSTRACT FROM AUTHOR]

Tumor cells have a modified glycosylation profile that promotes their evolution and/or their maintenance in the tumor. Sialylation is a type of glycosylation that is often altered in cancers. RNA-Seq database analysis revealed that the sialyltransferase gene ST3GAL2 is significantly overexpressed at all stages of colorectal cancer (CRC). ST3GAL2 sialylates both glycoproteins and glycolipids. The aim of this work was to investigate the involvement of ST3GAL2 in CRC. Using the HT29 tumor cell line derived from a stage II of CRC, we decreased the expression of ST3GAL2 by specific shRNA, and then characterized these cells by performing functional tests. We found that ST3GAL2 knock down (KD) significantly decreases tumor cell proliferation, cell migration and invasiveness properties in vitro . The cell cycle of these cells is affected with a change in cell cycle distribution and an increase of cell apoptosis. The effect of ST3GAL2 KD was then studied in vivo , following xenografts into nude mice, in which the tumor progression was significantly reduced. This work demonstrates that ST3GAL2 is a major player in the behavior of colorectal tumor cells, by modifying the sialylation state of glycoproteins and glycolipids which remain to be specifically identified., Competing Interests: None., (AJCR Copyright © 2022.)