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; 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.

克尔曼博士旨在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氏病（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，广告会影响加拿大的两个方面：生活质量降低和负担过高的医疗保健系统。为了满足有效的AD治疗的迫切需求，原始和创新的研究计划将加速抗氧化多酚作为AD疗法的研究。拟议的研究计划集中于在存在生物测量值（铁，铜和锌）的情况下进行多酚（Gallic Acid，Elagic Acid，Okadaic Acid） - 蛋白质（tau，淀粉样蛋白-Beta和载脂蛋白E4）相互作用。该程序的四个目标是研究多酚与生物标志物蛋白之间的相互作用，测量了多酚的抗氧化特性，脂质和DNA氧化的检测以及细胞内ROS形成的研究。椅子的目的是使用多种分析工具（包括电化学和光谱技术）在生物识别暴露之前和之后从人类神经元细胞中产生活性氧（ROS）的速率。该研究计划的新颖性将基于发现某些多酚是否可以防止生物识别诱导的神经毒性，减少ROS产生并在AD样病理氧化应激条件下保持细胞氧化还原电位。多学科研究计划将阐明抗氧化剂多酚的可能治疗作用，并探索生物妇女图在AD中的作用。此外，生物电化学平台将促进未来的其他小分子来治疗AD的研究。这项工作的预期意义是扩大治疗方向以促进新药物的开发，从而提供有效且安全的治疗方法。该研究计划的结果将为广告个体提供更好的前景，通过减轻广告相关的成本来使加拿大经济受益，并将加拿大尤其是安大略省的定位，并作为生物传感器研究的领导者，并培训了下一代加拿大研究才能。