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

项目摘要/摘要 最近发表在《科学》杂志上的一篇报告揭示了如何减少糖化应激和预防糖尿病的形成 高级糖基化终末产物(AGEs)将提高生物弹性并降低 发展中的帕金森氏症(PD)。糖的降解和代谢导致活性物质的产生 羰基物种，主要是甘油醛、乙二醛和甲基乙二醛，能自发地与氨基和 核酸。这些反应导致蛋白质功能不正常和DNA损伤，从而导致 各种与衰老相关的退行性疾病的进展，包括血管僵硬，神经变性， 肾病和癌症(1-6)。最近，一种酶的缺乏与早发性帕金森氏症有关 疾病DJ-1被发现具有乙草酸酶和脱甘糖活性，解毒活性羧基和修复 糖化鸟嘌呤(7-11)。重要的是，这些酶似乎只作用于早期糖基化产物，一次 形成的高级糖基化终末产物(AGEs)非常稳定，很容易积累。自由年龄约束于 并激活AGEs受体(RAGE)，它有许多与氧化有关的信号级联 应激、炎症和细胞增殖(12，13)。这些发现揭示了进化的 控制自发性糖基化反应和缓解的意义和潜在的治疗价值 年龄暴露和积累。天然产物，清除活性羰基，保护易受伤害的胺 减少RAGE激活是实现这些目标和提高生物复原力的可行候选者。 虽然在西方的饮食中基本不存在，但海洋大型藻类一直是人类的主要组成部分 历史上的饮食，包括世界上一些最健康的人群--比如蓝区 冲绳(14-16)。今天，水产养殖是食品生产和大型藻类生产中增长最快的部门。 在解决粮食安全和环境退化问题方面具有明显的潜力 全球人口增长(17，18)。因此，已经超过咖啡、茶叶和 按吨位计算，巧克力产量预计只会上升。因此，对潜在的效用进行调查 藻类衍生产品值得优先考虑。食用藻类的化学多样性与普通藻类不同。 陆生植物和相对未被开发的。藻类植物化学物质潜在用途的早期调查 用于控制糖化应激是有希望的，但缺乏关键的机制细节和活体可行性评估 (19、20)。目前，还没有FDA批准的针对糖化压力或年龄的疗法或补充剂 编队以提高生物复原力或控制相关病理。我们假设可食用的海豹 藻类将成为控制糖化压力的新疗法的丰富来源，并将 防止年龄形成。

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.