LCN2 Human, Pichia

NGAL is characterized by its three-dimensional barrel structure, which contains a ligand-binding site known as the calyx . This site allows receptors to attach to the surface of membranes, facilitating the formation of larger molecular complexes . NGAL is involved in the innate immune response by sequestering iron and preventing its use by bacteria, thereby limiting bacterial growth . It binds to bacterial siderophores as well as the mammalian siderophore 2,5-dihydroxybenzoic acid (2,5-DHBA), ensuring that excess free iron does not accumulate in the cytoplasm .

NGAL is a crucial biomarker for kidney injury. Due to its protease resistance and low molecular weight, it is excreted and detectable in urine . Injured epithelial cells in the kidney secrete a monomeric form of NGAL, while activated neutrophils secrete a dimeric form . This distinction is hypothesized to improve acute kidney injury (AKI) diagnostics by differentiating NGAL of inflammatory origin from that of renal origin . NGAL levels are elevated in both blood and urine within two hours of kidney injury and are predictive of dialysis need . Additionally, NGAL is associated with chronic kidney disease, contrast-induced nephropathy, kidney transplant outcomes, and mortality .

The recombinant production of human NGAL in Pichia pastoris (a species of yeast) is a common method for obtaining this protein for research and therapeutic purposes. Pichia pastoris is favored for its ability to perform post-translational modifications similar to those in higher eukaryotes, making it an ideal system for producing recombinant proteins . The recombinant NGAL produced in Pichia is used in various studies to understand its structure, function, and potential therapeutic applications .

Recent research has highlighted the potential of NGAL as a therapeutic target for neurodegenerative diseases. Under neuroinflammatory stress conditions, NGAL is produced and secreted by activated microglia and reactive astrocytes . It exerts neurotoxicity when secreted from reactive astrocytes, making it a target for strategies aimed at minimizing neuroinflammation and neuronal cell death . These strategies include regulating NGAL production at the transcriptional, posttranscriptional, and posttranslational levels, as well as blocking its functions using neutralizing antibodies or antagonists of its receptor .