Protein carbamylation in neurodegeneration and other age-related disorders

Abstract

Ageing is a complex process that is greatly influenced by environmental and genetic factors. Ageing at the cellular and molecular level is characterized by the accumulation of post-translationally modified proteins that are derogative to cells, termed Degenerative protein modification (DPM). A particular class of DPM, occurring under the impact of urea, termed brain ureido degenerative post-translational modifications (uDPM) has also been implicated in the molecular pathogenesis of Alzheimer's disease and related neurodegenerative disorders. These modifications can disrupt normal protein functions by altering their conformation, enzymatic activities, receptor recognitions, and physiological capabilities. Carbamylation is an age-related uDPM that results from the non-enzymatic modification of amino groups of ε-amino groups on lysine in proteins. The significance of carbamylation in some age-related disorders such as cataracts, rheumatoid arthritis,and cardiovascular diseases is well documented. However, the role of carbamylation in the pathogenesis of various neurodegenerative disorders, which are also age-dependent, has not been explored much. The aim of the current article is a retrospection of carbamylation, its effect on proteins, and its implications in ageing and neurodegenerative diseases. Carbamylation is one such age-related uDPM, which results from the non-enzymatic modification of amino groups of ε-amino groups on lysines or N-terminal amino groups present in proteins or peptides by isocyanate. The significance of carbamylation in some age-related disorders such as cataracts, rheumatoid arthritis, and cardiovascular diseases is well documented. However, the role of carbamylation in the pathogenesis of various neurodegenerative disorders, which are also age-dependent, has not been explored much. This mini-review will focus on the relationship between carbamylation and neurodegenerative disorders and provide an overview of the process of carbamylation, its contribution towards molecular ageing of protein, and the involvement of carbamylation in neurodegeneration and related diseases associated with ageing.