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Advanced glycation endproducts and their pathogenic roles in neurological disorders

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Abstract

Glycation is implicated in neurological disorders. In some cases it plays a key role in the pathogenesis, in others it plays a co-adjuvant role or it appears as a consequence of degenerative changes and protein accumulation stemming from other pathways. In this work, we attempt to provide a concise, updated review of the major recent findings concerning glycation in neurological diseases. After a short introduction covering advanced glycation endproducts (AGEs) and the receptor for AGEs (RAGE), we will discuss the impact of glycation in central nervous system disorders including Alzheimer’s, Parkinson’s and Creutzfeldt–Jakob disease, as well as peripheral diabetic polyneuropathies. Therapies directed at lowering the concentrations of RAGE ligands including AGEs, blocking RAGE signaling, preventing oxidative stress or lowering methylglyoxal (MGO) levels may significantly decrease the development of AGE-related pathologies in patients with neurological disorders. Many drugs are on the pipeline and the future clinical trials will reveal if the promising results translate into clinical application.

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Acknowledgments

This work was supported by the National Health and Medical Research Council (NHMRC), the J.O. and J.R. Wicking Foundation and Alzheimer’s Australia.

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  1. Molecular Medicine Research Group, Department of Pharmacology, School of Medicine, University of Western Sydney, Campbelltown, NSW, 2560, Australia

    Gerald Münch & Bernadette Westcott

  2. Glycation, Oxidation and Disease Laboratory, Touro University-California, Vallejo, USA

    Teresita Menini & Alejandro Gugliucci

  3. Department of Pharmacology, School of Medicine, University of Western Sydney, Locked Bag 1797, Penrith South DC, NSW, 1797, Australia

    Gerald Münch

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  1. Gerald Münch
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  2. Bernadette Westcott
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Correspondence to Gerald Münch.

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Münch, G., Westcott, B., Menini, T. et al. Advanced glycation endproducts and their pathogenic roles in neurological disorders. Amino Acids 42, 1221–1236 (2012). https://doi.org/10.1007/s00726-010-0777-y

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