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

免费核磁共振和生物测定指导筛选可食用海藻中的 AGE 抑制剂，以控制糖化应激并降低神经退行性变的风险。

• 批准号: 10329892
• 负责人: George Steven Hanna
• 金额: $ 4.42万
• 依托单位: MEDICAL UNIVERSITY OF SOUTH CAROLINA
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-17 至 2023-08-16
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10329892
• 关键词: Address; Advanced Glycosylation End Products; Aging; Albumins; Algae; Amines; Amino Acids; Animal Model; Antioxidants; Aquaculture; Binding; Biological; Biological Assay; Blood Glucose; Blood Vessels; Cataract; Cell Proliferation; Cell model; Chemicals; Chocolate; Chronic Disease; Coffee; Collagen; Column Chromatography; Consumption; Crude Extracts; DNA Damage; Data; Degenerative Disorder; Diet; Disease; Drug Kinetics; Environment; Enzyme-Linked Immunosorbent Assay; Enzymes; Ethanol; FDA approved; Farming environment; Filtration; Food production; Fructose; Genetic; Glucose; Glyceraldehyde; Glyoxal; Goals; Guanine; Hexanes; Human; In Vitro; Inflammation; Inflammatory; Investigation; Kidney Diseases; Knowledge; Lactoylglutathione Lyase; Lead; Libraries; Link; Literature; Longevity; Malignant Neoplasms; Measures; Metabolism; Methods; Modernization; Mus; Natural Products; Nerve Degeneration; Neurodegenerative Disorders; Nucleic Acids; Oxidative Stress; PARK7 gene; Parkinson Disease; Pathology; Physiological; Phytochemical; Plants; Population; Production; Proteins; Pyruvaldehyde; Reaction; Reactive Oxygen Species; Recording of previous events; Reporting; Research; Risk; Route; Sampling; Science; Serum; Signal Transduction; Solvents; Source; Specimen; Stress; Structure; Structure-Activity Relationship; Taxonomy; Tea; Therapeutic; Time; Toxic effect; Urine; Validation; base; computerized tools; design; dietary; dietary control; dosage; early onset; enzyme activity; extracellular; food security; glycation; improved; in vitro activity; in vivo; inhibitor/antagonist; innovation; macromolecule; metabolomics; novel; novel therapeutics; prevent; protein function; receptor for advanced glycation endproducts; repair enzyme; repaired; resilience; screening; small molecule; spectroscopic data; stem; sugar; voucher; western diet

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.

项目概要/摘要 《科学》杂志最近的一篇报告揭示了如何减少糖化应激并防止糖化应激的形成 高级糖基化终产物 (AGE) 将提高生物弹性并降低以下风险： 帕金森病 (PD) 的糖降解和代谢会导致反应性物质的产生。 羰基物质，主要是甘油醛、乙二醛和甲基乙二醛，它们自发地与氨基和 这些反应会导致蛋白质功能异常和 DNA 损伤，从而导致 各种与衰老相关的退行性疾病的进展，包括血管硬化、神经退行性变、 最近，一种酶的缺乏与早发性帕金森病有关。 疾病DJ-1被发现具有乙二醛酶和脱糖酶活性，可以解毒反应性羰基并修复 重要的是，这些酶似乎只作用于早期糖化产物一次。 形成的高级糖基化终末产物 (AGE) 高度稳定且易于与游离 AGE 结合。 并激活 AGE 受体 (RAGE)，该受体具有许多与氧化相关的信号级联 这些发现揭示了进化的过程。 控制自发糖化反应和减轻的意义和潜在治疗价值 AGE 暴露和积累的天然产物可清除活性羰基，保护脆弱的胺。 和减少 RAGE 激活是实现这些目标和提高生物弹性的可行候选者。 尽管西方饮食中基本上不存在海洋大型藻类，但它们一直是人类饮食的主要组成部分。 整个饮食历史，包括世界上一些最健康人群的饮食——例如蓝色区域 如今，水产养殖是食品生产和大型藻类生产中增长最快的部门。 具有解决粮食安全和环境退化问题的独特潜力 全球人口不断增加 (17, 18)，其结果是，大型藻类的产量已经超过了咖啡、茶和藻类。 巧克力产量预计只会上升，因此，对巧克力的潜在效用进行调查。 值得优先考虑的藻类衍生产品。食用藻类的化学多样性与藻类的化学多样性不同。 陆生植物和对藻类植物化学物质潜在用途的早期研究相对较少。 用于控制糖化应激的方法很有希望，但缺乏关键的机制细节和体内活力评估 (19, 20) 目前，尚无 FDA 批准的针对糖化应激或 AGE 的治疗方法或补充剂。 我们勇敢地面对可食用的海洋生物。 藻类将成为控制糖应激和新疗法的丰富来源 防止 AGE 形成。