Insulin-regulated aminopeptidase (IRAP) (IRAP)

The AT4 receptor, now molecularly identified as Insulin-regulated aminopeptidase (IRAP), is a transmembrane zinc-dependent metalloprotease that plays a dual role as an enzyme and a binding site for angiotensin IV. It is highly expressed in brain regions associated with cognition, such as the hippocampus and cortex, where it regulates the half-life of various neuropeptides including vasopressin, oxytocin, and somatostatin. Beyond its enzymatic role, IRAP is localized in GLUT4-containing vesicles and is translocated to the cell surface in response to insulin, thereby playing a role in glucose uptake. IRAP has emerged as a significant therapeutic target for neurodegenerative disorders like Alzheimer's disease because its inhibition or modulation leads to enhanced cognitive performance and memory consolidation. Small-molecule ligands and peptides targeting this receptor are currently being investigated for their ability to promote synaptogenesis and provide neuroprotection by augmenting the activity of endogenous neuropeptide systems or growth factor signaling pathways.

Other names

Angiotensin IV receptorAT4 receptorLeucyl-cystinyl aminopeptidaseLNPEPPlacental leucine aminopeptidaseP-LAPOxytocinaseCystinyl aminopeptidase

Drugs targeting this molecule typically act as competitive inhibitors of its enzymatic activity, preventing the degradation of memory-enhancing neuropeptides like vasopressin and oxytocin. In the case of small-molecule mimics like Dihexa, the interaction may also involve the potentiation of hepatocyte growth factor (HGF) signaling via its receptor c-Met.