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

Abstract

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.

Authors+Show Affiliations

Department of Experimental Neurodegeneration, Center for Biostructural Imaging of Neurodegeneration, University Medical Center Göttingen, Göttingen, Germany.Department of Experimental Neurodegeneration, Center for Biostructural Imaging of Neurodegeneration, University Medical Center Göttingen, Göttingen, Germany.Department of Experimental Neurodegeneration, Center for Biostructural Imaging of Neurodegeneration, University Medical Center Göttingen, Göttingen, Germany. Max Planck Institute for Experimental Medicine, Göttingen, Germany. Institute of Neuroscience, The Medical School, Newcastle University, Newcastle upon Tyne, United Kingdom.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31322580

Citation

Brás, Inês Caldeira, et al. "Glycation in Huntington's Disease: a Possible Modifier and Target for Intervention." Journal of Huntington's Disease, 2019.
Brás IC, König A, Outeiro TF. Glycation in Huntington's Disease: A Possible Modifier and Target for Intervention. J Huntingtons Dis. 2019.
Brás, I. C., König, A., & Outeiro, T. F. (2019). Glycation in Huntington's Disease: A Possible Modifier and Target for Intervention. Journal of Huntington's Disease, doi:10.3233/JHD-190366.
Brás IC, König A, Outeiro TF. Glycation in Huntington's Disease: a Possible Modifier and Target for Intervention. J Huntingtons Dis. 2019 Jul 16; PubMed PMID: 31322580.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Glycation in Huntington's Disease: A Possible Modifier and Target for Intervention. AU - Brás,Inês Caldeira, AU - König,Annekatrin, AU - Outeiro,Tiago Fleming, Y1 - 2019/07/16/ PY - 2019/7/20/pubmed PY - 2019/7/20/medline PY - 2019/7/20/entrez KW - Huntington’s disease KW - advanced glycation end products KW - diabetes mellitus KW - glycation KW - huntingtin JF - Journal of Huntington's disease JO - J Huntingtons Dis N2 - 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. SN - 1879-6400 UR - https://www.unboundmedicine.com/medline/citation/31322580/Glycation_in_Huntington's_Disease:_A_Possible_Modifier_and_Target_for_Intervention L2 - https://content.iospress.com/openurl?genre=article&id=doi:10.3233/JHD-190366 DB - PRIME DP - Unbound Medicine ER -