Chai Siew Yeen, Yeatman Holly R, Parker Michael W, Ascher David B, Thompson Philip E, Mulvey Hayley T, Albiston Anthony L
Howard Florey Institute, The University of Melbourne, Parkville, Victoria 3010, Australia.
BMC Neurosci. 2008 Dec 3;9 Suppl 2(Suppl 2):S14. doi: 10.1186/1471-2202-9-S2-S14.
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.
人们发现，肽类物质血管紧张素IV和LVV-血啡肽7在多项记忆任务中可增强记忆，并逆转实验性诱导记忆丧失动物的行为缺陷。这些肽特异性结合胰岛素调节氨肽酶（IRAP），该酶被认为是大脑中介导这些肽记忆效应的位点。然而，其作用机制尚不清楚，但可能涉及抑制IRAP的氨肽酶活性，因为血管紧张素IV和LVV-血啡肽7都是该酶的竞争性抑制剂。IRAP还有另一个功能域，被认为可调节胰岛素反应性葡萄糖转运蛋白GLUT4的转运，从而影响细胞对葡萄糖的摄取。尽管这些肽增强记忆的确切机制尚待阐明，但IRAP仍是开发新型认知增强剂的一个有前景的靶点。
