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Glycation in Huntington’s Disease: A Possible Modifier and Target for Intervention

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, gl...

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Autores principales: Brás, Inês Caldeira, König, Annekatrin, Outeiro, Tiago Fleming
Formato: Online Artículo Texto
Lenguaje:English
Publicado: IOS Press 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6839463/
https://www.ncbi.nlm.nih.gov/pubmed/31322580
http://dx.doi.org/10.3233/JHD-190366
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author Brás, Inês Caldeira
König, Annekatrin
Outeiro, Tiago Fleming
author_facet Brás, Inês Caldeira
König, Annekatrin
Outeiro, Tiago Fleming
author_sort Brás, Inês Caldeira
collection PubMed
description 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.
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spelling pubmed-68394632019-11-20 Glycation in Huntington’s Disease: A Possible Modifier and Target for Intervention Brás, Inês Caldeira König, Annekatrin Outeiro, Tiago Fleming J Huntingtons Dis Review 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. IOS Press 2019-08-27 /pmc/articles/PMC6839463/ /pubmed/31322580 http://dx.doi.org/10.3233/JHD-190366 Text en © 2019 – IOS Press and the authors. All rights reserved https://creativecommons.org/licenses/by-nc/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution Non-Commercial (CC BY-NC 4.0) License (https://creativecommons.org/licenses/by-nc/4.0/) , which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Review
Brás, Inês Caldeira
König, Annekatrin
Outeiro, Tiago Fleming
Glycation in Huntington’s Disease: A Possible Modifier and Target for Intervention
title Glycation in Huntington’s Disease: A Possible Modifier and Target for Intervention
title_full Glycation in Huntington’s Disease: A Possible Modifier and Target for Intervention
title_fullStr Glycation in Huntington’s Disease: A Possible Modifier and Target for Intervention
title_full_unstemmed Glycation in Huntington’s Disease: A Possible Modifier and Target for Intervention
title_short Glycation in Huntington’s Disease: A Possible Modifier and Target for Intervention
title_sort glycation in huntington’s disease: a possible modifier and target for intervention
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6839463/
https://www.ncbi.nlm.nih.gov/pubmed/31322580
http://dx.doi.org/10.3233/JHD-190366
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