Studying the mechanisms and targets of glycation and advanced glycation end-products in simple eukaryotic model systems.

Abstract

Biological systems are usually astonishingly complex. This complexity makes it often difficult if not impossible to study their inner workings. In order to address complex research questions more simply structured models (e.g., microorganisms, plants, non-vertebrate animals) are utilized. Findings from these studies can then be translated to more complex systems like mammals. This strategy facilitates the identification of relevant 'leads' that can be specifically addressed in the higher organism. In this review studies to elucidate the relevance, modes of action and molecular targets of reactive carbonyl species using simple model systems are discussed. These dicarbonyls are formed during metabolic activity in all organisms as toxic by-products that lead to the dysfunction of essential cellular components by a process termed glycation, resulting ultimately in the generation of advanced glycation end-products. Understanding how both dicarbonyls and advanced glycation end-products are formed, which environmental conditions influence their levels and what cellular pathways they affect is paramount to develop efficient strategies targeting diseases that are related to reactive carbonyl species, like diabetes, neurodegenerative disorders and cancer. This contribution presents important findings in the field of dicarbonyls and glycation from fungi, plants, the nematode Caenorhabditis elegans and the fruit fly Drosophila melanogaster.