Plant-made RAGE; a research tool for diabetes
Advanced Glycation End products (AGEs) are a chemically heterogenous group of compounds formed via the Maillard Reaction. AGEs have a key role in the development and progression of diabetic complications. In addition, the production and accumulation of AGEs has been implicated in a range of other diseases including Alzheimer’s disease, atherosclerosis, tumour growth and metastases. The pathogenic activity of AGEs is partly mediated by activation of multi-ligand AGE receptors. The best known is the receptor for AGEs (RAGE), a 55-kDa protein belonging to the immunoglobulin superfamily, which is expressed in both membrane-bound (tRAGE) and soluble isoforms. Circulating soluble RAGE (sRAGE) is a truncated isoform that does not contain the effector domain, but is able to bind ligands with a similar affinity to tRAGE. Consequently, sRAGE may be considered a natural competitive antagonist to tRAGE. This activity has been elegantly exploited by researchers who have used sRAGE to attenuate AGE-dependent processes including atherosclerosis, metastasis and progressive nephropathy.
Soluble RAGE (sRAGE) is an important novel agent for the prevention of diabetic complications. Clinical translation of this research will require safe large-scale production of sRAGE. The hypothesis of this proposal is that plants are a viable production system for rapid, large-scale, inexpensive manufacture of functional sRAGE.
Funding Support: Juvenile Diabetes Research Foundation