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Lookup NU author(s): Professor Tiago OuteiroORCiD
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC 4.0).
© 2019-IOS Press and the authors. All rights reserved.Glycation is the non-enzymatic reaction between reactive dicarbonyls and amino groups, and gives rise to a variety of different reaction products known as advanced glycation end products (AGEs). Accumulation of AGEs on proteins is inevitable, and is associated with the aging process. Importantly, glycation is highly relevant in diabetic patients that experience periods of hyperglycemia. AGEs also play an important role in neurodegenerative diseases including Alzheimer's (AD) and Parkinson's disease (PD). Huntington's disease (HD) is a hereditary neurodegenerative disease caused by an expansion of a CAG repeat in the huntingtin gene. The resulting expanded polyglutamine stretch in the huntingtin (HTT) protein induces its misfolding and aggregation, leading to neuronal dysfunction and death. HD patients exhibit chorea and psychiatric disturbances, along with abnormalities in glucose and energy homeostasis. Interestingly, an increased prevalence of diabetes mellitus has been reported in HD and in other CAG triplet repeat disorders. However, the mechanisms underlying the connection between glycation and HD progression remain unclear. In this review, we explore the possible connection between glycation and proteostasis imbalances in HD, and posit that it may contribute to disease progression, possibly by accelerating protein aggregation and deposition. Finally, we review therapeutic interventions that might be able to alleviate the negative impact of glycation in HD.
Author(s): Bras IC, Konig A, Outeiro TF
Publication type: Review
Publication status: Published
Journal: Journal of Huntington's Disease
Year: 2019
Volume: 8
Issue: 3
Pages: 245-256
Online publication date: 27/08/2019
Acceptance date: 02/04/2018
ISSN (print): 1879-6397
ISSN (electronic): 1879-6400
Publisher: IOS Press
URL: https://doi.org/10.3233/JHD-190366
DOI: 10.3233/JHD-190366
PubMed id: 31322580
