NEU4

Last update 08 May 2025

Basic Info

Synonyms

N-acetyl-alpha-neuraminidase 4, NEU4, neuraminidase 4

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Introduction

Exo-alpha-sialidase that catalyzes the hydrolytic cleavage of the terminal sialic acid (N-acetylneuraminic acid, Neu5Ac) of a glycan moiety in the catabolism of glycolipids, glycoproteins and oligosacharides. Efficiently hydrolyzes gangliosides including alpha-(2->3)-sialylated GD1a and GM3 and alpha-(2->8)-sialylated GD3 (PubMed:15213228, PubMed:15847605, PubMed:21521691). Hydrolyzes poly-alpha-(2->8)-sialylated neural cell adhesion molecule NCAM1 likely at growth cones, suppressing neurite outgrowth in hippocampal neurons (By similarity). May desialylate sialyl Lewis A and X antigens at the cell surface, down-regulating these glycan epitopes recognized by SELE/E selectin in the initiation of cell adhesion and extravasation (PubMed:21521691). Has sialidase activity toward mucin, fetuin and sialyllactose (PubMed:15847605).

100 Clinical Results associated with NEU4

100 Translational Medicine associated with NEU4

0 Patents (Medical) associated with NEU4

Literatures (Medical) associated with NEU4

01 Dec 2024·Alzheimer's & Dementia

Microglial and neuronal subpopulations associated with cognitive resilience to amyloid deposition in genetically diverse mice

Article

Author: Howell, Gareth R ; Uyar, Asli ; Carter, Gregory W ; Bloss, Erik B ; Heuer, Sarah E ; Skelly, Daniel A

AbstractBackgroundData from human and model organism studies suggest that genetic background influences susceptibility and resilience to Alzheimer’s Disease (AD) neuropathology. We previously showed that, wild‐derived PWK/PhJ (PWK) mice carrying the APP/PS1 transgene (PWK.APP/PS1) exhibit cognitive and synaptic resilience compared to traditionally‐studied B6.APP/PS1 inbred mice in presence of amyloid beta (Aβ) plaque deposition. PWK.APP/PS1 mice also contain different proportions of transcriptionally‐defined microglia compared to B6.APP/PS1. The precise molecular mechanisms underlying these differences between strains remain unknown. In this study, we aim to identify and characterize cell populations in the hippocampi of genetically distinct B6 and PWK mouse strains, and investigate cell‐type specific gene expression patterns associated with cognitive resilience in presence of amyloid deposition.MethodWe generated cohorts of B6.APP/PS1 and PWK.APP/PS1 transgenic female mice and wild‐type (WT) littermates as controls (n = 4 per strain/genotype group). At 8 months of age mice were euthanized, hippocampi collected, and single nuclear RNA sequencing (snRNAseq) was performed using 10x Genomics Chromium platform. Seurat R package (version 5.0.1) was used for major data analysis.ResultWe identified subpopulations of microglial cells characterized by varying expression patterns of a set of genes including Hk2, Itgam and Dock8. Neuronal subtypes were clustered by top marker genes Plk5 and Adarb2. Oligodendrocytes, oligodendrocyte progenitor cells, and endothelial cells were marked by expression of Mog, Neu4 and Abcc9, respectively. Differential expression and pathway enrichment analysis revealed strain‐specific immune and cell signaling pathways altered in distinct cell populations in response to amyloid pathogenesis. Cross‐species mapping of these transcriptomic signatures with human hippocampal gene modules identified AD‐relevant molecular mechanisms observed in mouse models of AD at the cell‐type level.ConclusionThis study suggests that cell‐type specific transcriptomic response to amyloid is modulated by genetic background and our findings re‐iterate the importance of incorporating genetic diversity to model phenotypic and molecular heterogeneity in AD. Since the nuclei enriched in this dataset are enriched for neurons, future interrogations will provide evidence for specific neuronal populations and molecular mechanisms that differentiate cognitively resilient PWK from susceptible B6 mice, providing insights into mechanisms that can be leveraged to promote AD resilience.

27 Nov 2024·Oncogene

NEU4-mediated desialylation enhances the activation of the oncogenic receptors for the dissemination of ovarian carcinoma

Article

Author: Wang, Longlong ; Qu, Pengpeng ; Yang, Shuang ; Li, Jia ; Wang, Shuo ; Tian, Baorui ; Liu, Yanhua ; Wang, Shufan ; Zhou, Rui ; Shi, Jie ; Liu, Yuxin ; Mu, Yuhao ; Yan, Jie ; Shao, Xintao ; Chen, Yanan ; Wei, Ding ; Hu, Taoyu ; Shi, Yi

Glycosylation profoundly influences the interactions between cancer cells and microenvironmental stromal cells during the peritoneal disseminated metastasis of ovarian carcinoma (OC), which is the major cause of cancer-related death. Although the characteristic cancer glycoconjugates are widely used as biomarkers for cancer diagnosis, our knowledge about cancer glycome remains quite fragmented due to the technique limitations in analyzing glycan chains with tremendous structural and functional heterogeneity. Given the dysregulated cancer glycome is defined by the altered glycosylation machinery, here we performed a systematic loss-of-function screen on 498 genes involved in glycosylation for key regulators of OC dissemination. We identified neuraminidase 4 (NEU4), an enzyme capable of hydrolyzing terminal sialic acid from glycoconjugates, as a vital peritoneal dissemination-promoting modifier of OC glycome. In human patients with high-grade serous OC (HGSOC), increased NEU4 was detected in the disseminated OC cells when compared with that in the primary tumor cells, which significantly correlated with the worse survival. Among three alternative splice-generated isoforms of human NEU4, we revealed that only the plasma membrane-localized NEU4 isoform 2 (NEU4-iso2) and intracellular isoform 3 promoted the peritoneal dissemination of OC by enhancing the cell motility and epithelial-mesenchymal transition. We also identified NEU4-iso2-regulated cell surface glycoproteome and found that NEU4-iso2 desialylated the epithelial growth factor receptor (EGFR), in particular at N¹⁹⁶ residue, for the hyperactivation of EGFR and its downstream tumor-promoting signaling cascades. Our results provide new insights into how the OC glycome is dysregulated during OC progression and reveal a functionally important glycosite on EGFR for its abnormal activation in cancer.

01 Oct 2024·Advanced Science

Targeting Neuraminidase 4 Attenuates Kidney Fibrosis in Mice

Article

Author: Dai, Cai‐Xia ; Jiang, Li‐Long ; Xiao, Ping‐Ting ; Kuang, Yu‐Jia ; Xie, Zhi‐Shen ; Rong, Xiao‐Ling ; Hao, Jin‐Hua ; Chen, Qian‐Qian ; Liu, E‐Hu ; Zhang, Lei

AbstractDespite significant progress in therapy, there remains a lack of substantial evidence regarding the molecular factors that lead to renal fibrosis. Neuraminidase 4 (NEU4), an enzyme that removes sialic acids from glycoconjugates, has an unclear role in chronic progressive fibrosis. Here, this study finds that NEU4 expression is markedly upregulated in mouse fibrotic kidneys induced by folic acid or unilateral ureter obstruction, and this elevation is observed in patients with renal fibrosis. NEU4 knockdown specifically in the kidney attenuates the epithelial‐to‐mesenchymal transition, reduces the production of pro‐fibrotic cytokines, and decreases cellular senescence in male mice. Conversely, NEU4 overexpression exacerbates the progression of renal fibrosis. Mechanistically, NEU4254‐388aa interacts with Yes‐associated protein (YAP) at WW2 domain (231‐263aa), promoting its nucleus translocation and activation of target genes, thereby contributing to renal fibrosis. 3,5,6,7,8,3ʹ,4ʹ‐Heptamethoxyflavone, a natural compound, is identified as a novel NEU4 inhibitor, effectively protecting mice from renal fibrosis in a NEU4‐dependent manner. Collectively, the findings suggest that NEU4 may represent a promising therapeutic target for kidney fibrosis.

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NEU4

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