Key result
Angiotensin IV and LVV-hemorphin-7 enhance memory via competitive IRAP inhibition.
Why the study?
The role of the angiotensin AT(4) receptor and its ligands in enhancing learning and memory and reversing memory deficits in animal models was investigated.
IRAP inhibition merits exploration as a memory target; animal data leave open human translation and safety.
The angiotensin AT(4) receptor was originally defined as the specific, high affinity binding site for the hexapeptide angiotensin IV (Ang IV). Subsequently, the peptide LVV-hemorphin 7 was also demonstrated to be a bioactive ligand of the AT(4) receptor. Central administration of Ang IV or LVV-hemorphin 7 (LVV-H7) markedly enhances learning and memory in normal rodents and reverse memory deficits observed in animal models of amnesia. The high affinity binding site has a broad distribution in the brain including areas such as the hippocampus that are involved in memory processing. The high affinity Ang IV binding site (AT(4) receptor) has been identified as the transmembrane enzyme, insulin-regulated membrane aminopeptidase (IRAP). Insulin-regulated aminopeptidase is a type II integral membrane spanning protein belonging to the M1 family of aminopeptidases and in insulin-responsive cells colocalizes with GLUT4 in specific intra-cellular vesicles. Both Ang IV and LVV-H7 are competitive inhibitors of IRAP catalytic activity and are not substrates of the enzyme.
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Albiston et al. (2004) conducted a review in Memory loss / Alzheimer's disease. Angiotensin IV and LVV-hemorphin-7 was evaluated. Angiotensin IV and LVV-hemorphin-7 enhance learning and memory by acting as competitive inhibitors of insulin-regulated aminopeptidase (IRAP), presenting a potential therapeutic target for memory loss.
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