Toxicity of Protein and DNA-AGEs in Neurodegenerative Diseases (NDDs) with Decisive Approaches to Stop the Deadly Consequences

Protein and DNA-advanced glycation end-products (DNA-AGEs) are toxic by-products of metabolism and are also assimilated by high temperature processed foods. AGEs may be generated rapidly or over long times stimulated by distinct triggering mechanisms, thereby accounting for their roles in multiple settings and disease states. Neurodegenerative diseases (NDDs) are associated with the misfolding and deposition of specific proteins, DNA adduct formation either intra or extra-cellularly in the nervous system. There is also evidence that brain tissue in patients with NDD is exposed to DNA oxidation and glycoxidation during the course of the disease. Although familial mutations play an important role in protein misfolding and aggregation, the majority of cases of NDD are sporadic, suggesting that other factors must contribute to the onset and progression of these disorders. High levels of refined and carbohydrate enriched diets, hyper caloric diets and sedentary lifestyles drive endogenous formation of AGEs via accumulation of highly reactive glycolysis intermediates and activation of the reductase pathway (polyol/aldose) producing high intracellular reducing sugars are the important modifiable environmental factors. Some of these modifications might affect proteins in detrimental ways and lead to their misfolding and accumulation. Reducing sugars play important roles in modifying proteins, forming AGEs in a non-enzymatic process named glycation. Several proteins linked to NDDs, such as amyloid β, tau, prions and transthyretin, were found to be glycated in patients, and this is thought to be associated with increased protein stability through the formation of crosslinks that stabilize protein aggregates causing NDDs like Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), familial amyloid polyneuropathy (FAP), and prion disease (PrD). Moreover, glycation may also be responsible, via the receptor for AGE (RAGE), for an increase in oxidative stress and inflammation through the formation of reactive oxygen species (ROS) and the induction of nuclear factor-κB (NF-κB). Here, we revised the role of protein and DNA-AGEs in the major NDDs and highlight the potential value of protein and DNA-AGEs glycation as a biomarker or target for therapeutic intervention. Additionally, the chapter covers several new therapeutic approaches that have been applied to treat these devastating disorders, including the use of various synthetic, natural and gold and silver conjugated nanoparticles (Au, Ag-NPs).