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Glycation vs. glycosylation: a tale of two different chemistries and biology in Alzheimer’s disease

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Abstract

In our previous studies, we reported that the activity of an anti-oxidant enzyme, Cu,Zn-superoxide dismutase (Cu,Zn-SOD) became decreased as the result of glycation in vitro and in vivo. Glycated Cu,Zn-SOD produces hydroxyl radicals in the presence of transition metals due to the formation of a Schiff base adduct and a subsequent Amadori product. This results in the site-specific cleavage of the molecule, followed by random fragmentation. The glycation of other anti-oxidant enzymes such as glutathione peroxidase and thioredoxin reductase results in a loss or decrease in enzyme activity under pathological conditions, resulting in oxidative stress. The inactivation of anti-oxidant enzymes induces oxidative stress in aging, diabetes and neurodegenerative disorders. It is well known that the levels of Amadori products and Ne-(carboxylmethyl)lysine (CML) and other carbonyl compounds are increased in diabetes, a situation that will be discussed by the other authors in this special issue. We and others, reported that the glycation products accumulate in the brains of patients with Alzheimer’s disease (AD) patients as well as in cerebrospinal fluid (CSF), suggesting that glycation plays a pivotal role in the development of AD. We also showed that enzymatic glycosylation is implicated in the pathogenesis of AD and that oxidative stress is also important in this process. Specific types of glycosylation reactions were found to be up- or downregulated in AD patients, and key AD-related molecules including the amyloid-precursor protein (APP), tau, and APP-cleaving enzymes were shown to be functionally modified as the result of glycosylation. These results suggest that glycation as well as glycosylation are involved in oxidative stress that is associated with aging, diabetes and neurodegenerative diseases such as AD.

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Acknowledgments

This work is partially supported by Grants in aid from the Ministry of Education, Culture, Sports, Science and Technology and from Japan Society for Promotion of Science. The authors thank Ms. Fumi Ota for her help with preparing and submitting this paper and Dr. Milton Feather for his help with the English editing.

This paper is dedicated to the late Professor Gérard Siest, University of Lorraine, Nancy, who passed away on April 9, 2016.

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Authors and Affiliations

  1. Systems Glycobiology Research Group, RIKEN-Max Planck Joint Research Center for Systems Chemical Biology, Global Research Cluster, RIKEN, 2-1 Hirosawa, Wako, Saitama, 351-0198, Japan

    Naoyuki Taniguchi, Yasuhiko Kizuka & Shinobu Kitazume

  2. Department of Biochemistry, Sapporo Medical University School of Medicine, South-1 West-17, Chuo-ku, Sapporo, 060-8556, Japan

    Motoko Takahashi

  3. Department of Systems Pharmacology and Translational Therapeutics, Center for Translational Targeted Therapeutics and Nanomedicine of the Institute for Translational Medicine and Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA

    Vladimir V. Shuvaev

  4. Laboratory of Biochemistry, School of Pharmacy, Hyogo University of Health Sciences, 1-3-6 Minatojima, Chuo-ku, Kobe, Hyogo, 650-8530, Japan

    Tomomi Ookawara

  5. Department of Cellular and Molecular Neuropathology, Juntendo University School of Medicine, Hongo 2-1-1, Bunkyou-ku, Tokyo, 113-8421, Japan

    Akiko Furuta

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  1. Naoyuki Taniguchi
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  4. Shinobu Kitazume
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Correspondence to Naoyuki Taniguchi.

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Naoyuki Taniguchi and Motoko Takahashi contributed equally to this review.

A part of this work was presented as a plenary lecture in the 12th International Symposium on the Maillard reaction symposium held in Tokyo in September 1–3, 2015.

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Taniguchi, N., Takahashi, M., Kizuka, Y. et al. Glycation vs. glycosylation: a tale of two different chemistries and biology in Alzheimer’s disease. Glycoconj J 33, 487–497 (2016). https://doi.org/10.1007/s10719-016-9690-2

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  • DOI: https://doi.org/10.1007/s10719-016-9690-2

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