Protein synthesis offer clues to memory loss

A new method of identifying proteins as they are created in the body could offer insight into why learning and memory becomes impaired in Alzheimer’s disease. Using Caenorhabditis elegans as a model, scientists at the University of Queensland developed a process using amino acids generated in new proteins to identify them as they are synthesised. The proteins were tagged to enable scientists determine whether they are created in response to internal stimuli, such as regular cell activity, or external stimuli, such as learning activities. “Our protocol circumvents this limitation by identifying de novo–synthesised proteins via the incorporation of the chemically modifiable azidohomoalanine instead of the natural amino acid methionine in the nascent protein, followed by facilitating the visualisation of the resulting labelled proteins in situ,” Professor Jürgen Götz, Foundation Chair of Dementia Research at the Queensland Brain Institute, told Laboratory News. “Azidohomoalanine is a noncanonical amino acid that contains a unique bio-orthogonal chemical motif, an azide group, which is absent in the cells of organisms ranging from C. elegans to vertebrates. These highly reactive groups (an azide group in the case of azidohomoalanine) can be made to react in what is termed ‘click-chemistry’ with a fluorescent tag or with biotin that is fused to a linker molecule, provided that these molecules are coupled to a reactive alkyne group.” It is believed proteins play a key role in learning and memory formation because their composition changes during these processes, but their exact function and identity remains a mystery. Götz said this new method will help determine which molecules are newly synthesised in learning and memory retrieval, and whether there are specific impairment unique to Alzheimer’s. “When we know which memory molecules are not formed or formed to a lower degree during memory formation and retrieval we can develop strategies to boost the formation of these molecules,” Götz said.