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This article is part of the supplement: Proceedings of the 8th International Conference on Alzheimer's Disease Drug Discovery

Open Access Review

Development of cognitive enhancers based on inhibition of insulin-regulated aminopeptidase

Siew Yeen Chai12*, Holly R Yeatman12, Michael W Parker34, David B Ascher4, Philip E Thompson5, Hayley T Mulvey5 and Anthony L Albiston1

Author Affiliations

1 Howard Florey Institute, The University of Melbourne, Parkville, Victoria 3010, Australia

2 Centre for Neuroscience, The University of Melbourne, Parkville, Victoria 3010, Australia

3 Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, Victoria 3010, Australia

4 St Vincent's Institute of Medical Research, Fitzroy, Victoria 3065, Australia

5 Department of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences, Monash University, Parkville, Victoria 3052, Australia

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BMC Neuroscience 2008, 9(Suppl 2):S14  doi:10.1186/1471-2202-9-S2-S14

Published: 3 December 2008

Abstract

The peptides angiotensin IV and LVV-hemorphin 7 were found to enhance memory in a number of memory tasks and reverse the performance deficits in animals with experimentally induced memory loss. These peptides bound specifically to the enzyme insulin-regulated aminopeptidase (IRAP), which is proposed to be the site in the brain that mediates the memory effects of these peptides. However, the mechanism of action is still unknown but may involve inhibition of the aminopeptidase activity of IRAP, since both angiotensin IV and LVV-hemorphin 7 are competitive inhibitors of the enzyme. IRAP also has another functional domain that is thought to regulate the trafficking of the insulin-responsive glucose transporter GLUT4, thereby influencing glucose uptake into cells. Although the exact mechanism by which the peptides enhance memory is yet to be elucidated, IRAP still represents a promising target for the development of a new class of cognitive enhancing agents.