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.

项目摘要/摘要 科学的最新报告揭示了如何减少糖性压力并防止形成 高级糖基化终产（年龄）将提高生物弹性，并降低 发展帕金森氏病（PD）。糖降解和代谢导致反应性产生 羰基物种，原发性甘油醛，乙二醛和甲基乙醛，它们与氨基和氨基反应 核酸。这些反应导致蛋白质功能和DNA损伤不当，导致 各种衰老相关的退化性疾病的进展，包括血管僵硬，神经退行性疾病， 肾病和癌症（1-6）。最近，一种酶与早期发作的帕金森氏症有关 发现疾病，DJ-1具有乙二醇酶和脱脂酶活性，排毒反应性羰基和修复 糖化鸟嘌呤（7-11）。重要的是，这些酶似乎仅对早期糖化产品作用 形成的高级糖基化终产物（年龄）是高度稳定的，并且很容易积累。自由年龄结合到 并激活年龄的接收器（RAGE），该接收器具有许多与氧化有关的信号级联 压力，炎症和细胞增殖（12，13）。这些发现揭示了进化 控制赞助反应和缓解的重要性和潜在的治疗价值 年龄暴露和积累。清除反应性羰基的天然产品，保护脆弱的胺 减少愤怒激活是实现这些目标并提高生物弹性的可行候选者。 尽管西方饮食中大部分不存在，但海洋大藻一直是人类的主要组成部分 整个历史上的饮食，包括世界上一些最健康的人群的饮食 - 例如蓝色区域 冲绳（14-16）。如今，水产养殖是粮食生产和大藻生产的增长最快的领域 与解决粮食安全和环境退化问题有关 全球人口不断上升（17，18）。结果，大型阿尔加尔的生产已经超过咖啡，茶和 吨位生产巧克力，只预计只会上升。那使投资投资于 藻类得出的产品优先级的脂肪。可食藻的化学多样性与 陆生植物和相对不流动的植物。早期研究藻类生理化学物质的潜在使用 有望用于控制糖性应力，但缺乏体内的关键机械细节和生存能力评估 （19，20）。目前，尚无针对糖性压力或年龄的FDA批准的治疗剂或补充剂 形成以提高生物弹性或控制相关病理。我们假设可食用的海洋 藻类将作为控制糖性胁迫和 防止年龄形成。