Traumatization of neurospheres for elicitation of tau aggregation in their constituent neurons

损伤神经球以引发其组成神经元中的 tau 蛋白聚集

• 批准号: 492049-2015
• 负责人: Yadav, VikramadityaGanapati
• 金额: $ 1.82万
• 依托单位: University of British Columbia
• 依托单位国家: 加拿大
• 项目类别: Engage Grants Program
• 财政年份: 2015
• 资助国家: 加拿大
• 起止时间: 2015-01-01 至 2016-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=587175
• 关键词: Traumatization; neurospheres; elicitation; tau; aggregation

The treatment of neurodegenerative diseases such as Alzheimer's disease (AD), chronic traumatic encephalopathy (CTE) and frontotemporal dementia (FTD) is an urgent national priority. However, there are no known therapies against these diseases. Drug discovery in this category has been stymied by the absence of reliable screening tools for evaluating the performance of drug candidates before they are tested on human patients in clinical trials. Specifically, the model systems employed by the pharmaceutical industry to screen drug candidates do not accurately recapitulate the microenvironment of a degenerated human brain. To this end, our research group at the University of British Columbia, in collaboration with scientists from STEMCELL Technologies Inc., proposes to apply principles and methodologies of tissue engineering to construct a faithful and accurate mimic a degenerated human brain for use as a drug screening platform. Specifically, the current proposal seeks to develop and validate a key step in the construction of the model organ - the elicitation of neurodegeneration in otherwise healthy brain tissue, and we will employ recent insights about biochemical similarities and dissimilarities between AD, CTE and FTD to achieve our goal. We anticipate that the current project will lay the foundations for the eventual development of an organoid biomanufacturing platform that will be integrated into the pharmaceutical industry's existing drug discovery infrastructure.

治疗神经退行性疾病，例如阿尔茨海默氏病（AD），慢性创伤性脑病（CTE）和额叶痴呆症（FTD）是紧迫的国家优先事项。但是，没有针对这些疾病的已知疗法。由于缺乏可靠的筛查工具来评估候选药物在临床试验中对人类患者进行测试之前，该类别中的药物发现受到了困扰。具体而言，制药行业用于筛查药物候选物的模型系统并未准确地概括退化的人脑的微环境。为此，我们在不列颠哥伦比亚大学的研究小组与STEMCELL Technologies Inc.的科学家合作，建议采用组织工程的原理和方法，以构建忠实而准确的模仿人类大脑作为药物筛查平台。具体而言，当前的提案旨在开发和验证模型器官构建的关键步骤 - 在其他健康的脑组织中神经退行性的启发，我们将采用有关AD，CTE和FTD之间的生物化学相似性和差异的最新见解，以实现我们的目标。我们预计当前的项目将为最终开发器官生物制造平台开发基础，该平台将集成到制药行业现有的药物发现基础设施中。