NEU1

What is NEU1 Protein?

NEU1 gene (neuraminidase 1) is a protein coding gene which situated on the short arm of chromosome 6 at locus 6p21. NEU1 is an enzyme that plays a role inside cells, specifically in lysosomes. It is responsible for catalyzing the hydrolysis of sialoglycoside bonds, thus participating in the metabolism of glycoproteins and glycolipids. The function of NEU1 is not limited to its degradation but also involves the regulation of physiological processes, such as lysosomal exosomes by controlling the sialic acid content of lysosomal associated membrane protein 1 (LAMP1). The NEU1 protein is consisted of 415 amino acids and NEU1 molecular weight is approximately 45.5 kDa.

What is the Function of NEU1 Protein?

The NEU1 protein, known as neuraminidase 1, performs a critical function as an enzyme within the lysosomal system of cells. NEU1 initiates the breakdown of sialoglycoconjugates by removing their terminal sialic acids. Sialic acids are a family of carbohydrate derivatives that often terminate the glycan chains of glycoproteins and glycolipids. NEU1 also regulates the physiological process of lysosomal exocytosis, which is the release of lysosomal contents outside the cell. The activity and compartmentalization of NEU1 within lysosomes depend on its interaction with the auxiliary protein, protective protein/cathepsin A (PPCA). This interaction is necessary for the catalytic activation of NEU1.

NEU1 Related Signaling Pathway

NEU1 not only acts as a decomposing enzyme, but is also involved in the regulation of cell signaling. It has been shown to interact with a variety of receptors, regulating their levels of sialylation and thus affecting signaling pathways. NEU1 is involved in signaling for A variety of receptors, including the elastin receptor complex, insulin receptor, integrin β4, TLR4, Trk A receptor, PDGF-BB and IGF receptors, EGF and MUC1 receptors, and CD31 receptors. Studies have suggested that NEU1 may play a therapeutic potential in Alzheimer's disease through the immune system. Activation of NEU1 may prompt macrophages to shift to the M2 state, which helps reduce toxic amyloid oligomers. The function of NEU1 on the cell membrane is different from its function in the lysosome. On the cell membrane, NEU1 may be regulated through its phosphorylated C-terminal and participate in signaling processes. Some parts of NEU1 exist in a specific topology on the cell membrane and have the ability to dimerize. This structural feature may be critical to NEU1's signaling function.

NEU1 Related Diseases

NEU1 protein is a lysosomal associated acidic ceramidase that has been implicated in a variety of diseases. Deletion or mutation of the NEU1 protein can lead to the accumulation of ceramides in cells, which can lead to a range of diseases, such as Sandhof disease, Gilbert syndrome and Fabre disease. These diseases can manifest as neurological symptoms, liver problems, kidney problems, heart problems, and skin problems.

Fig1. Therapeutic potential of Neu1 in Alzheimer's disease via the immune system. (Aiza Khan, 2021)

Bioapplications of NEU1

Given its role in many diseases, NEU1 has become a good target for disease treatment and research. It has been shown that NEU1 regulates viral replication by controlling sialylation levels of coronavirus nucleocapsid proteins, so NEU1 inhibitors may be a potential treatment to limit SARS-CoV-2 replication. In terms of drug development, studies have screened out active ingredients with kidney protection, such as salvianolic acid B, which plays an anti-renal fibrosis role by targeting NEU1. In hepatocellular carcinoma, high expression of NEU1 is associated with poor prognosis and may play a role by regulating tumor-related pathways and immune function.

Case Study 1: Ekaterina P Demina, 2021

Elevated levels of plasma sialic acid, heightened activity of neuraminidase, and a decrease in the sialic acid content of sialic acid low-density lipoproteins (LDLs) have previously been linked to atherosclerosis and coronary artery disease in humans. However, the process behind this connection has not yet been thoroughly examined. Researchers explored the possibility that neuraminidases play a role in atherosclerosis development by cleaving sialic acid from the glycan chains of LDL glycoproteins and glycolipids.
This study focused on the progression of atherosclerosis in mice that lack apolipoprotein E and LDL receptors, and that have a genetic absence of neuraminidases 1, 3, and 4, or were administered specific neuraminidase inhibitors. We discovered that the removal of sialic acid from LDL glycoprotein, apolipoprotein B 100, by human neuraminidases 1 and 3, boosts the engulfment of human LDL by macrophages in culture and within aortic root lesions in Apoe-/- mice, through asialoglycoprotein receptor 1. Furthermore, the genetic deactivation or medicinal blockade of neuraminidases 1 and 3 considerably postponed the emergence of fatty streaks in the aortic root. This effect occurred independently of alterations in plasma cholesterol and LDL levels in the Apoe-/- and Ldlr-/- mouse models of atherosclerosis.

Fig1. Liquid chromatography–mass spectrometry (LC-MS) profiles of ApoB N-glycans from neuraminidase-treated and untreated human LDL.

Fig2. Monoclonal rabbit antibody against neuraminidase 1 (NEU1).

Case Study 2: Xiaoman Zhou, 2020

Sialidases are responsible for removal of sialic acids from glycoproteins and glycolipids. Sialic acid modification in bladder cancer tissue was determined by lectin blot. The down-regulation of NEU1 in bladder cancer cells was determined by high resolution liquid chromatography mass spectrometry (HR LC-MS). The effects of sialidase NEU1 expression on proliferation and apoptosis of human bladder cancer cells were examined by western blot, RT-PCR, confocal imaging and flow cytometry. Moreover, the function of sialic acids on fibronectin-integrin α5β1 interaction were assayed by immunoprecipitation and ELISA. The results showed that Downregulation of NEU1 was primarily responsible for aberrant expression of sialic acids in bladder cancer cells. NEU1 disrupted FN-integrin α5β1 interaction and deactivated the Akt signaling pathway.

Fig3. HCV29, KK47, and J82 cells were treated with 5 ng/mL TGFβ for 48 h.

Fig4. Lectin blotting assay.

NEU1 has several biochemical functions, for example, exo-alpha-(2->3)-sialidase activity,exo-alpha-(2->6)-sialidase activity,exo-alpha-(2->8)-sialidase activity. Some of the functions are cooperated with other proteins, some of the functions could acted by NEU1 itself. We selected most functions NEU1 had, and list some proteins which have the same functions with NEU1. You can find most of the proteins on our site.

NEU1 has direct interactions with proteins and molecules. Those interactions were detected by several methods such as yeast two hybrid, co-IP, pull-down and so on. We selected proteins and molecules interacted with NEU1 here. Most of them are supplied by our site. Hope this information will be useful for your research of NEU1.

GLB1;JUNB;EEF1A1;tktA;pi3p;ELN;Rcc1;VAPA