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The role of advanced glycation end products in various types of neurodegenerative disease: a therapeutic approach


Protein glycation is initiated by a nucleophilic addition reaction between the free amino group from a protein, lipid or nucleic acid and the carbonyl group of a reducing sugar. This reaction forms a reversible Schiff base, which rearranges over a period of days to produce ketoamine or Amadori products. The Amadori products undergo dehydration and rearrangements and develop a cross-link between adjacent proteins, giving rise to protein aggregation or advanced glycation end products (AGEs). A number of studies have shown that glycation induces the formation of the β-sheet structure in β-amyloid protein, α-synuclein, transthyretin (TTR), copper-zinc superoxide dismutase 1 (Cu, Zn-SOD-1), and prion protein. Aggregation of the β-sheet structure in each case creates fibrillar structures, respectively causing Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, familial amyloid polyneuropathy, and prion disease. It has been suggested that oligomeric species of glycated α-synuclein and prion are more toxic than fibrils. This review focuses on the pathway of AGE formation, the synthesis of different types of AGE, and the molecular mechanisms by which glycation causes various types of neurodegenerative disease. It discusses several new therapeutic approaches that have been applied to treat these devastating disorders, including the use of various synthetic and naturally occurring inhibitors. Modulation of the AGE-RAGE axis is now considered promising in the prevention of neurodegenerative diseases. Additionally, the review covers several defense enzymes and proteins in the human body that are important anti-glycating systems acting to prevent the development of neurodegenerative diseases.



amyloid beta


Alzheimer’s disease


alkylformyl glycosylpyrroles




advanced glycation end products




arginine lysine imidazole


amylolateral sclerosis


711-alagebrium chloride


amyloid precursor protein


bovine spongiform encelopathy


cluster of differentiation 36


Creutzfeldt-Jakob disease



Cu, Zn-SOD-1:

copper-zinc superoxide dismutase 1


diethylenetriaminepentaacetic acid




(−)-epigallocatechin gallate


familial amyloid polyneuropathy




glyceraldehyde-3-phosphate dehydrogenase


glyoxal lysine dimer




glycogen synthase kinase-3




isoferulic acid


Lewy bodies


leucine-rich repeat kinase 2




methylglyoxal lysine dimer

MSR type II:

macrophage scavenger receptor types II


nicotinamide adenine dinucleotide phosphate


nuclear factor-κB


neurofibrillary tangles


origanum majorana




Parkinson’s disease




cellular prion protein


phenacylthiazolium bromide


receptor of advanced glycation end products


reactive oxygen species


synuclein alpha


soluble receptor of advanced glycation end products






tumor necrosis factor-α


thiamine pyrophosphate


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Salahuddin, P., Rabbani, G. & Khan, R.H. The role of advanced glycation end products in various types of neurodegenerative disease: a therapeutic approach. Cell Mol Biol Lett 19, 407–437 (2014).

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  • Aggregation
  • Advanced glycation end products
  • Glycation in Alzheimer’s disease
  • Glycation in Parkinson’s disease
  • Glycation in amyotrophic lateral sclerosis
  • Glycation in familial amyloid polyneuropathy
  • Glycation in prion diseases
  • Glyoxylases
  • AGE inhibitors