The chemical language of protein glycation

Glycation is a non-enzymatic post-translational modification (PTM) that is correlated with many diseases, including diabetes, cancer and age-related disorders. Although recent work points to the importance of glycation as a functional PTM, it remains an open question whether glycation has a causal role in cellular signaling and/or disease development. In this Review, we contextualize glycation as a specific mechanism of carbon stress and consolidate what is known about advanced glycation end-product (AGE) structures and mechanisms. We highlight the current understanding of glycation as a PTM, focusing on mechanisms for installing, removing or recognizing AGEs. Finally, we discuss challenges that have hampered a more complete understanding of the biological consequences of glycation. The development of tools for predicting, modulating, mimicking or capturing glycation will be essential for interpreting a post-translational glycation network. Therefore, continued insights into the chemistry of glycation will be necessary to advance understanding of glycation biology.