Neu3, a sialidase, is one of four mammalian sialidases. Sialidases catalyze the removal of α -glycosidically linked sialic acid residues from glycoproteins and glycolipids, initiating the degradation of these glycoconjugates. Neu3, associated with the plasma membrane, modulates transmembrane signaling by regulating gangliosides and is involved in many biological processes [1].

In mouse models, Neu3 has been shown to be crucial in several disease-related processes. In pulmonary fibrosis, Neu3-/-mice had significantly less inflammation, less upregulation of profibrotic cytokines and other sialidases, and less fibrosis after bleomycin-induced injury, indicating its necessity for full-blown pulmonary fibrosis [4]. Recombinant murine Neu3 induced inflammation and fibrosis in mouse lungs, with male mice showing a more pronounced effect, suggesting its sufficiency in promoting fibrosis [2]. In GM1 gangliosidosis, Glb1/Neu3 double KO mice had a shorter lifespan, increased neurodegeneration, and a higher GM1 ganglioside to GA1 glycolipid ratio compared to Glb1 KO mice, highlighting Neu3's role in GM1 ganglioside catabolism [3]. In bladder cancer, siRNA-mediated knockdown of Neu3 in cell lines revealed its contribution to cancer invasiveness, as it activates ERK and PI3K signaling [5].

In conclusion, Neu3 is essential in processes like ganglioside modulation, and its role has been clearly demonstrated through gene knockout mouse models in diseases such as pulmonary fibrosis, GM1 gangliosidosis, and bladder cancer. These models have provided valuable insights into the biological functions of Neu3 and its potential as a therapeutic target in these disease areas.