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

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

Publication date: Jul 16, 2019

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.

Br’es, I.C., K”onig, A., and Outeiro, T.F. Glycation in Huntington’s Disease: A Possible Modifier and Target for Intervention. 06584. 2019 J Huntingtons Dis.

Concepts Keywords
Aging Trinucleotide repeat disorder
Alzheimer Ages
Chorea Neurodegeneration
Diabetes Mellitus Advanced glycation end-product
Diabetic Glycation
Energy Homeostasis Huntingtin
Enzymatic Senescence
Gene Biomolecules
Glucose Posttranslational modification
Glycation Branches of biology
Huntingtin Huntington’s disease
Huntington Important neurodegenerative diseases
Hyperglycemia Prevalence diabetes mellitus
Misfolding Chorea
Neurodegenerative HD hereditary neurodegenerative
Neurodegenerative Diseases Neuronal dysfunction
Parkinson Reaction products


Type Source Name
disease MESH disease progression
disease MESH diabetes mellitus
disease DOID diabetes mellitus
drug DRUGBANK D-glucose
drug DRUGBANK Dextrose unspecified form
disease MESH abnormalities
disease DOID chorea
disease MESH chorea
disease MESH death
disease MESH hereditary neurodegenerative disease
disease MESH neurodegenerative diseases
pathway BSID Neurodegenerative Diseases
disease DOID hyperglycemia
disease MESH hyperglycemia
disease MESH aging
pathway BSID Aging


Original Article

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