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Targeting advanced glycation with pharmaceutical agents: where are we now?

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Abstract

Advanced glycation end products (AGEs) are the final products of the Maillard reaction, a complex process that has been studied by food chemists for a century. Over the past 30 years, the biological significance of advanced glycation has also been discovered. There is mounting evidence that advanced glycation plays a homeostatic role within the body and that food-related Maillard products, intermediates such as reactive α-dicarbonyl compounds and AGEs, may influence this process. It remains to be understood, at what point AGEs and their intermediates become pathogenic and contribute to the pathogenesis of chronic diseases that inflict current society. Diabetes and its complications have been a major focus of AGE biology due to the abundance of excess sugar and α-dicarbonyls in this family of diseases. While further temporal information is required, a number of pharmacological agents that inhibit components of the advanced glycation pathway have already showed promising results in preclinical models. These therapies appear to have a wide range of mechanistic actions to reduce AGE load. Some of these agents including Alagebrium, have translated successfully to clinical trials, while others such as aminoguanidine, have had undesirable side-effect profiles. This review will discuss different pharmacological agents that have been used to reduce AGE burden in preclinical models of disease with a focus on diabetes and its complications, compare outcomes of those therapies that have reached clinical trials, and provide further rationale for the use of inhibitors of the glycation pathway in chronic diseases.

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Acknowledgments

DJB was supported by National Health and Medical Research Council of Australia (NHMRC) Project and Diabetes Australia Research Program Grants. JMF was supported by a NHMRC Senior Research Fellowship. This research was supported by the NHMRC, Mater Foundation and JDRF International. The authors would like to thank Dr Tim Dargaville for creating the chemical structures of the AGE inhibitors. We would also like to acknowledge Dr Linda Gallo, Mrs Nicole Flemming and Mr Aowen Zhang for their editorial assistance.

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Authors and Affiliations

  1. Glycation and Diabetes, Mater Research Institute – The University of Queensland, Translational Research Institute, Woolloongabba, Australia

    Danielle J. Borg & Josephine M. Forbes

  2. Mater Clinical School, School of Medicine, University of Queensland, St Lucia, Australia

    Josephine M. Forbes

  3. Department of Medicine, The University of Melbourne, Austin Hospital, Heidelberg, Australia

    Josephine M. Forbes

  4. Baker IDI Heart and Diabetes Institute, Melbourne, Australia

    Josephine M. Forbes

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  1. Danielle J. Borg
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Correspondence to Josephine M. Forbes.

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Borg, D.J., Forbes, J.M. Targeting advanced glycation with pharmaceutical agents: where are we now?. Glycoconj J 33, 653–670 (2016). https://doi.org/10.1007/s10719-016-9691-1

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