The receptor for advanced glycation endproducts (RAGE) is a pattern-recognition receptor that belongs to the immunoglobin superfamily of cell surface proteins. This receptor binds with various chemically-distinct ligands, including amyloid-beta peptides. The interactions between the amyloid-beta peptide and RAGE accelerate several signaling cascades and produce proinflammatory mediators that play a role in several neurodegenerative diseases, including Alzheimer's disease. Diffusion is an important factor in how receptors function, yet the effect of amyloid-beta peptides on RAGE diffusion has not yet been studied. The purpose of this study is to measure the role of the two most prevalent amyloid-beta peptides, 1-40 and 1-42, in altering the lateral diffusion of RAGE as well as intracellular signal activation. Both amyloid-beta 1-40 and 1-42 peptides altered RAGE diffusion as measured by single particle tracking compared to the control RAGE-HEK293 cells that were not exposed to amyloid-beta peptides. Treatment with amyloid-beta 1-40 resulted in slower RAGE diffusion compared to the control, but slightly faster diffusion was observed for the treatment with amyloid-beta 1-42. Amyloid-beta 1-40 and 1-42 exhibit differences in conformation, oligomerization as well as binding mechanisms to RAGE. Differences in ligand-binding mechanisms for amyloid-beta 1-40 and 1-42 are suggested to be the reason they have different effects on RAGE diffusion despite the fact that they only differ by two amino acids.

Effect of amyloid-beta 1-40 and 1-42 peptides on the lateral diffusion and signaling of receptor for advanced glycation endproducts (RAGE)

ACS Fall 2021

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