Bioelectrochemistry of proteins

蛋白质的生物电化学

• 批准号: CRC-2021-00068
• 负责人: Kerman, Kagan
• 金额: $ 7.29万
• 依托单位: University of Toronto
• 依托单位国家: 加拿大
• 项目类别: Canada Research Chairs
• 财政年份: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=762186
• 关键词: Bioelectrochemistry; proteins

Dr. Kerman aims to develop a new generation of analytical methods and biosensors that would aid understanding the fundamental molecular interactions of "oxidative stress theory" in Alzheimer's disease (AD). As the leading form of dementia, AD impacts Canada from two fronts: diminishing quality of life and over-burdening the health care system. To address the urgent need for effective AD treatment, the original and innovative research program will accelerate the study of antioxidant polyphenols as AD therapeutics. The proposed research program is focused on the study of polyphenol (gallic acid, ellagic acid, okadaic acid)-protein (tau, amyloid-beta and apolipoprotein E4) interactions in the presence of biometals (iron, copper and zinc). The four objectives of the program are the study of the interaction between polyphenols and biomarker proteins, measuring the antioxidant properties of polyphenols, the detection of lipid and DNA oxidation and the study of intracellular ROS formation. The chair aims to compare the rate of reactive oxygen species (ROS) production from human neuronal cells before and after biometal exposure using a wide variety of analytical tools including electrochemical and spectroscopic techniques. The novelty of the research program will be based on discovering whether some of the polyphenols might prevent biometal-induced neurotoxicity, reduce ROS production, and maintain the cellular redox potential under AD-like pathological oxidative stress conditions. The multidisciplinary research program will shed light on the possible therapeutic effects of antioxidant polyphenols and explore the role of biometals in AD. Furthermore, the bioelectrochemical platform will facilitate future studies with other small molecules for the treatment of AD. The expected significance of the work is expanding the therapeutic directions to promote development of new medications, thereby providing effective and safe treatments. The results of this research program will offer better prospects for AD individuals, benefit Canadian economy by alleviating AD-associated costs, and position Canada, especially Ontario, as a leader in biosensor research with training of the next generation of Canadian research talents.

Kerman博士的目标是开发新一代的分析方法和生物传感器，以帮助理解阿尔茨海默病（AD）中“氧化应激理论”的基本分子相互作用。作为痴呆症的主要形式，AD从两个方面影响加拿大：生活质量下降和医疗保健系统负担过重。为了解决有效治疗AD的迫切需求，原创和创新的研究计划将加速抗氧化多酚作为AD治疗剂的研究。拟议的研究计划的重点是研究多酚（没食子酸，鞣花酸，冈田酸）-蛋白质（tau，淀粉样蛋白-β和载脂蛋白E4）在生物金属（铁，铜和锌）存在下的相互作用。该计划的四个目标是研究多酚和生物标志物蛋白之间的相互作用，测量多酚的抗氧化特性，检测脂质和DNA氧化以及研究细胞内ROS的形成。主席的目的是使用各种分析工具，包括电化学和光谱技术，比较生物金属暴露前后人类神经元细胞的活性氧（ROS）产生速率。该研究计划的新颖性将基于发现一些多酚是否可以防止双酚A诱导的神经毒性，减少ROS的产生，并在AD样病理性氧化应激条件下维持细胞的氧化还原电位。该多学科研究计划将揭示抗氧化剂多酚的可能治疗作用，并探索生物金属在AD中的作用。此外，生物电化学平台将促进未来与其他小分子治疗AD的研究。这项工作的预期意义是扩大治疗方向，促进新药物的开发，从而提供有效和安全的治疗方法。该研究计划的结果将为AD患者提供更好的前景，通过减轻AD相关成本使加拿大经济受益，并通过培训下一代加拿大研究人才，使加拿大，特别是安大略省，成为生物传感器研究的领导者。