Complimentary NMR and Bio-Assay Guided Screening of Edible Marine Algae for AGE Inhibitors to Control Glycative Stress and Reduce Risk of Neurodegeneration.

点击翻译按钮获取中文摘要

Project Summary/Abstract A recent report in Science reveals how reducing glycative stress and preventing the formation of Advanced Glycation End-Products (AGEs) will improve biological resilience and reduce the risk of developing Parkinson’s Disease (PD). Sugar degradation and metabolism result in the production of reactive carbonyl species, primarily glyceraldehyde, glyoxal and methylglyoxal, that spontaneously react with amino and nucleic acids. These reactions lead to improper protein function and DNA damage that contribute to the progression of a variety of aging related degenerative diseases including vascular stiffening, neurodegeneration, nephropathy and cancer (1-6). Recently, an enzyme whose deficiency is associated with early-onset Parkinson’s Disease, DJ-1, was found to have glyoxalase and deglycase activity, detoxifying reactive carbonyls and repairing glycated guanine (7-11). Importantly, these enzymes only appear to act on early-stage glycation products, once formed, Advanced Glycation End Products (AGEs) are highly stable and readily accumulate. Free AGEs bind to and activate the receptor for AGEs (RAGE), which has a number of signaling cascades relevant to oxidative stress, inflammation and cellular proliferation (12, 13). These discoveries reveal both the evolutionary significance and the potential therapeutic value of controlling spontaneous glycation reactions and mitigating AGE exposure and accumulation. Natural products that scavenge reactive carbonyls, protect vulnerable amines and reduce RAGE activation are viable candidates to achieve these goals and improve biological resilience. Although largely absent from the Western Diet, marine macroalgae have been a major component of the human diet throughout history, including those of some of the healthiest populations in the world-- such as the Blue Zone of Okinawa (14-16). Today, aquaculture is fastest growing sector of food production and macroalgae production has distinct potential for addressing both food security and environmental degradation problems associated with rising global populations (17, 18). As a result, macroalgal production, which already surpasses coffee, tea and chocolate production by tonnage, is only expected to rise. Thus, making investigations into the potential utility of algae derived products worthy of prioritization. The chemical diversity of edible algae is distinct from that of terrestrial plants and relatively underexplored. Early investigations into the potential use of algal phytochemicals for controlling glycative stress are promising but lack key mechanistic details and viability assessments in vivo (19, 20). Currently, there are no FDA-approved therapeutics or supplements targeting glycative stress or AGE formation to improve biological resilience or control related pathologies. We hypothesize that edible marine algae will serve as a plentiful source for novel therapeutics for controlling glycative stress and preventing AGE formation.