Title:Glycation-induced Amyloid Formation in Proteins: An Emerging
Perspective to Explore Diabetes Associated Onset of Neurodegenerative
Symptoms
Volume: 20
Issue: 1
Author(s): Samudra Prosad Banik*
Affiliation:
- Department of Microbiology, Maulana Azad College, Kolkata 700013, India
Keywords:
Advanced glycation end product, protein aggregation, amyloid plaques, diabetes, neurodegenerative disorders, arteriosclerosis.
Abstract: Non-enzymatic protein glycation occurs spontaneously via the formation of sugarprotein
Schiff adducts. The end products of this pathway are terminally misfolded proteins popularly
known as Advanced Glycation End (AGE) Products. Glycated proteins account for a diverse
spectrum of physiological maladies including arteriosclerosis, renal failure, diabetic complications,
obesity, and neurological disorders. AGEs not only jeopardise the functionality of
modified proteins but also induce the formation of Covalent protein cross-links. Glycation has
the potential to induce the unfolding and refolding of globular proteins into cross-β structures
thus resembling many amyloid deposits like amyloid beta, tau protein, and prions. However,
glycation-induced amyloid formation is not a generic property of proteins; instead, it is guided by
the nature and conformation of the protein, the type of glycation agent as well as the solution
conditions governing the glycation reaction. The half-lives of AGE adducts are prolonged by
their impaired proteasomal clearance since glycation modifies the lysine residues and renders
them unavailable for ubiquitination. AGEs are cleared via sequestration with specific cell surface
receptors (RAGE); subsequently, downstream signalling events involving MAPK and NF-κB
result in the activation of inflammatory response or the apoptotic pathway. This perspective article
discusses the current developments in understanding the various facets of glycationassociated
protein aggregation and the corresponding development of amyloid-like entities.
