Sialidase-3 (NEU3) (NEU3)

Human sialidase NEU3, also known as Sialidase-3, is a plasma membrane-associated enzyme that plays a pivotal role in the catabolism of gangliosides by removing terminal sialic acid residues (UniProt, 2024; GeneCards, 2024). This enzymatic activity is a key regulator of cell surface signaling, influencing the function of major receptors such as the epidermal growth factor receptor (EGFR) and the insulin receptor (PubMed, 2022; NCBI Gene, 2024). NEU3 is frequently overexpressed in various malignancies, including colon, renal, and prostate cancers, where it contributes to tumor progression, cell survival, and metastasis (Amerigo Scientific, 2024; Wikipedia, 2024). Beyond oncology, NEU3 has been identified as a major driver of pulmonary and hepatic fibrosis by activating pro-fibrotic signaling loops and inactivating anti-fibrotic proteins (MDPI, 2021; ResearchGate, 2022). Conversely, its downregulation or deficiency is associated with metabolic disorders like obesity and type 2 diabetes, highlighting its complex role in maintaining insulin sensitivity (PubMed, 2015; Amerigo Scientific, 2024). Therapeutic strategies targeting NEU3 include small molecule inhibitors like DANA analogues and picolinates, which aim to mitigate its pro-tumorigenic and pro-fibrotic activities (J Med Chem, 2018; MDPI, 2021). However, drug development faces challenges in achieving selectivity over other human sialidases (NEU1, NEU2, and NEU4) to avoid off-target effects (J Med Chem, 2018). Additionally, the dual role of NEU3 in different pathologies necessitates careful patient selection and monitoring of metabolic biomarkers (PubMed, 2015; MDPI, 2021).

Other names

Neuraminidase 3 (GeneCards, 2024)Membrane sialidase (UniProt, 2024)Ganglioside sialidase (PMC, 2012)N-acetyl-alpha-neuraminidase 3 (GeneCards, 2024)SIAL3 (Wikipedia, 2024)

Inhibition of sialidase enzymatic activity to modulate ganglioside-mediated signaling and prevent pro-fibrotic or pro-tumorigenic pathways (MDPI, 2021; J Med Chem, 2018).