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.

Glycoprotein Pathways Altered in Frontotemporal Dementia With Autoimmune Disease

“…Given inflammation is considered a pathological hallmark of neurodegeneration, it is important to consider what affect this inflammatory response could have on adaptive immunity, particularly given adaptive immunity also serves to support the function of innate immunity and the dialogue between the two is critical and constant. In support of neurodegeneration driving these immune processes, variation in CSF glycan expression has been detected in multiple neurodegenerative diseases, including Alzheimer’s disease (AD), Parkinson’s disease, Huntington’s disease and amyotrophic lateral sclerosis ( 46 , 50 – 56 ). Our data adds bvFTD to this list of CNS diseases.…”

Advanced Glycation End Products (AGEs): Biochemistry, Signaling, Analytical Methods, and Epigenetic Effects

“…Numerous studies showed that the AGEs and the advanced lipoxidation end products (ALEs) are involved in the development and progression of chronic degenerative diseases, including diabetes [28][29][30], cardiovascular diseases [29,31,32], neurological disorder [33,34], some types of cancer [35,36], and all those pathologies in which the mechanisms of oxidative stress are involved, as well as the senescence processes [33].…”

Effect of Advanced Glycation End-Products and Excessive Calorie Intake on Diet-Induced Chronic Low-Grade Inflammation Biomarkers in Murine Models

“…The formation of AGEs by the Maillard reaction gained prominence in human health research during the 1950s, after the discovery of glycated hemoglobin under physiological conditions and its reported correlation with glycemic levels in diabetic patients [ 63 ]. The glycation of cellular proteins has a negative effect on cell and tissue function, molecular aging, and chronic disease development [ 64 , 65 ]. In addition to their endogenous occurrence, AGEs are also formed during the thermal processing of foods, significantly increasing humans’ exposure to dietary AGEs (dAGEs).…”

“…In addition to their endogenous occurrence, AGEs are also formed during the thermal processing of foods, significantly increasing humans’ exposure to dietary AGEs (dAGEs). Food-borne AGEs are part of a heterogeneous group of chemically stable molecules resulting from the Maillard reaction, some of which are implicated in benignly improving flavors, aromas, and browning, while others are thought to be involved in adverse health effects (e.g., chronic inflammation, degenerative diseases, aging, insulin resistance) [ 64 , 65 ].…”