ASGR1 Specific Neutra™ Antibody Products

The asialoglycoprotein receptor 1 (ASGR1), a major subunit of the asialoglycoprotein receptor (ASGR), is a cell surface receptor primarily found in the sinusoidal face of hepatocytes. Structurally, ASGR1 is a transmembrane protein consisting of a transmembrane domain, cytoplasmic domain, and extracellular carbohydrate recognition domain (CRD). It plays a crucial role in the clearance of circulating glycoproteins by recognizing and binding to terminal galactose residues on these molecules. It is characterized by its high specificity for binding desialylated glycoproteins and facilitating their endocytosis and degradation. Additionally, ASGR1 has been linked to various physiological and pathological processes, making it a promising target for therapeutic interventions in liver-related disorders and drug delivery systems.

Its Gene ID: 432, UniProtKB ID: P07306, and OMIM ID: 108360.

ASGR1 Signaling Pathways

Upon binding desialylated glycoproteins, ASGR1 internalizes via clathrin-coated pits and transports to early endosomes. From there, the receptor-ligand complex can follow different routes: recycling back to the cell surface for further ligand uptake, targeting lysosomes for degradation, or engaging in signaling cascades that modulate cellular functions such as the activation of protein kinases, modulation of gene expression, and regulation of cellular processes like proliferation or apoptosis. Additionally, ASGR1 signaling may intersect with pathways involved in endocytosis, lysosomal degradation, and recycling of the receptor-ligand complex. These signaling pathways are critical in cellular homeostasis, immune responses, and metabolic regulation in hepatocytes.

Fig.1 Mechanism and possible effects of downregulation of ASGR1.¹

ASGR1-Related Diseases

ASGR1 is implicated in various diseases due to its role in glycoprotein clearance and homeostasis. In liver diseases like hepatitis, cirrhosis, and hepatocellular carcinoma, altered ASGR1 expression affects glycoprotein metabolism, contributing to disease progression. In metabolic disorders such as diabetes, ASGR1 dysregulation influences glucose and lipid metabolism through interactions with key signaling pathways. Inherited disorders like ASGR deficiency can result in impaired glycoprotein metabolism and lead to systemic complications. Furthermore, ASGR1 expression changes have been observed in certain cancers, suggesting a potential role in tumor progression and metastasis.

Fig.2 An example of ASGR-targeted hepatocellular Carcinoma Treatment.²

Antibodies Targeting ASGR1

A neutralizing antibody targeting ASGR1 could offer a promising therapeutic strategy for diseases involving ASGR1 dysregulation. By binding to ASGR1 and blocking its interaction with ligands, such an antibody could inhibit the clearance of desialylated glycoproteins, potentially altering disease progression. Studies have proved an anti-ASGR single-chain antibody can bind the recombinant and native forms of the ASGR and could also promote ASGR-specific internalization of a B11-PE38KDEL immunotoxin and induce cell death. This targeted neutralization may offer a novel strategy for managing conditions such as viral hepatitis, liver fibrosis, and metabolic disorders by regulating the turnover of glycoproteins in hepatocytes. Moreover, the development of neutralizing antibodies against ASGR1 holds the potential for addressing liver-related complications in diverse pathological contexts, paving the way for innovative treatment modalities.

Creative Biolabs offers sixteen distinct types of anti-ASGR1 antibody products that may be utilized in different applications. These high-quality, reproducible recombinant antibodies will help you complete your research more efficiently.

REFERENCES

1. Zhao, Wenqi, Suowen Xu, and Jianping Weng. "ASGR1: an emerging therapeutic target in hypercholesterolemia." Signal Transduction and Targeted Therapy 8.1 (2023): 43.
2. Nair, Anroop B., et al. "Development of asialoglycoprotein receptor-targeted nanoparticles for selective delivery of gemcitabine to hepatocellular carcinoma." Molecules 24.24 (2019): 4566.