Glycoconjugate Journal

, Volume 33, Issue 4, pp 487–497 | Cite as

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

  • Naoyuki TaniguchiEmail author
  • Motoko Takahashi
  • Yasuhiko Kizuka
  • Shinobu Kitazume
  • Vladimir V. Shuvaev
  • Tomomi Ookawara
  • Akiko Furuta


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.


Glycation Maillard reaction Cu,Zn-SOD Glycosylation GnT-III Amyloid β-peptides BACE1 Alzheimer’s disease Oxidative stress Glyco-redox 



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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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Naoyuki Taniguchi
    • 1
    Email author
  • Motoko Takahashi
    • 2
  • Yasuhiko Kizuka
    • 1
  • Shinobu Kitazume
    • 1
  • Vladimir V. Shuvaev
    • 3
  • Tomomi Ookawara
    • 4
  • Akiko Furuta
    • 5
  1. 1.Systems Glycobiology Research Group, RIKEN-Max Planck Joint Research Center for Systems Chemical Biology, Global Research ClusterRIKENSaitamaJapan
  2. 2.Department of BiochemistrySapporo Medical University School of MedicineSapporoJapan
  3. 3.Department of Systems Pharmacology and Translational Therapeutics, Center for Translational Targeted Therapeutics and Nanomedicine of the Institute for Translational Medicine and TherapeuticsPerelman School of Medicine, University of PennsylvaniaPhiladelphiaUSA
  4. 4.Laboratory of Biochemistry, School of PharmacyHyogo University of Health SciencesKobeJapan
  5. 5.Department of Cellular and Molecular NeuropathologyJuntendo University School of MedicineTokyoJapan

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