Development of cognitive enhancers based on inhibition of insulin-regulated aminopeptidase
Siew Yeen Chai, Holly R Yeatman, Michael W Parker, David B Ascher, Philip E Thompson, Hayley T Mulvey, Anthony L Albiston
BMC NEUROSCIENCE | BMC | Published : 2008
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 gluc..View full abstract
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Awarded by NHMRC
DBA is an Australian Postgraduate Award Scholar and a recipient of a St Vincent's Institute Foundation Scholarship sponsored by Colin North and Major Engineering. MWP is an Australian Research Council Federation Fellow and a National Health and Medical Research Council (NHMRC) Honorary Fellow. SYC is an NHMRC Senior Research Fellow. HRY is supported by a Sylvia and Charles Viertel Alzheimer's Postgraduate Scholarship. This work is supported by the Alzheimer's Drug Discovery Foundation/Institute for the Study of Aging, Neurosciences Victoria, NHMRC Development grants (IDs: 454714 & 520695) and the CASS Foundation of Australia.