Journal article

Aryl Sulfonamide Inhibitors of Insulin-Regulated Aminopeptidase Enhance Spine Density in Primary Hippocampal Neuron Cultures

Shanti Diwakarla, Erik Nylander, Alfhild Gronbladh, Sudarsana Reddy Vanga, Yasmin Shamsudin Khan, Hugo Gutierrez-de-Teran, Jonas Savmarker, Leelee Ng, Pham Vi, Thomas Lundback, Annika Jenmalm-Jensen, Richard Svensson, Per Artursson, Sofia Zelleroth, Karin Engen, Ulrika Rosenstrom, Mats Larhed, Johan Aqvist, Siew Yeen Chai, Mathias Hallberg

ACS Chemical Neuroscience | AMER CHEMICAL SOC | Published : 2016

Abstract

The zinc metallopeptidase insulin regulated aminopeptidase (IRAP), which is highly expressed in the hippocampus and other brain regions associated with cognitive function, has been identified as a high-affinity binding site of the hexapeptide angiotensin IV (Ang IV). This hexapeptide is thought to facilitate learning and memory by binding to the catalytic site of IRAP to inhibit its enzymatic activity. In support of this hypothesis, low molecular weight, nonpeptide specific inhibitors of IRAP have been shown to enhance memory in rodent models. Recently, it was demonstrated that linear and macrocyclic Ang IV-derived peptides can alter the shape and increase the number of dendritic spines in h..

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University of Melbourne Researchers