New insights into the mechanisms of age-related protein-protein crosslinking in the human lens. (August 2021)

• Record Type: Journal Article
• Authors: Schey, Kevin L.; Wang, Zhen; Friedrich, Michael G.; Truscott, Roger J.W.
• Is Part Of: Experimental eye research. Volume 209(2021)
• Publication Date: 2021-08
• Subjects: Protein crosslinking -- Mass spectrometry -- Dehydroalanine -- Long-lived proteins -- Succinimide; Ophthalmology -- Periodicals; Eye -- Periodicals; Œil -- Périodiques; Ophthalmology; Periodicals; Electronic journals; 612.8405
• DOI: 10.1016/j.exer.2021.108679
• Languages: English
• ISSNs: 0014-4835

Abstract

Abstract: Although protein crosslinking is often linked with aging as well as some age-related diseases, very few molecular details are available on the nature of the amino acids involved, or mechanisms that are responsible for crosslinking. Recent research has shown that several amino acids are able to generate reactive intermediates that ultimately lead to covalent crosslinking through multiple non-enzymatic mechanisms. This information has been derived from proteomic investigations on aged human lenses and the mechanisms of crosslinking, in each case, have been elucidated using model peptides. Residues involved in spontaneous protein-protein crosslinking include aspartic acid, asparagine, cysteine, lysine, phosphoserine, phosphothreonine, glutamic acid and glutamine. It has become clear, therefore, that several amino acids can act as potential sites for crosslinking in the long-lived proteins that are present in aged individuals. Moreover, the lens has been an invaluable model tissue and source of crosslinked proteins from which to determine crosslinking mechanisms that may lead to crosslinking in other human tissues. Highlights: Review of crosslinking chemistry in proteins Summary of enzymatic and non-enzymatic crosslinking mechanisms Discussion of methods to detect protein crosslinks