In Vivo Screen for Neuroprotective Agents

神经保护剂的体内筛选

• 批准号: 6786447
• 负责人: Chuenlei Parng
• 金额: $ 15.98万
• 依托单位: PHYLONIX PHARMACEUTICALS, INC.
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-01 至 2005-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6786447
• 关键词: alternatives to animals in research; apoptosis; developmental neurobiology; disease /disorder model; drug discovery /isolation; drug screening /evaluation; embryo /fetus; embryo /fetus drug adverse effect; embryo /fetus pharmacology; embryogenesis; fluorescence microscopy; high throughput technology; model design /development; nervous system disorder chemotherapy; neural degeneration; neuropathology; neuroprotectants; nonhuman therapy evaluation; zebrafish

DESCRIPTION (provided by applicant): Aberrant apoptosis is implicated in several neurodegenerative disorders including, stroke, brain trauma, spinal cord injury, Parkinson's disease, amyotrophic lateral sclerosis (ALS), Alzheimer's and Huntington's disease. These neurodegenerative diseases are associated with high morbidity and mortality, and treatment options are limited. Agents that modulate apoptosis are a major focus of drug development efforts by biopharmaceutical companies. Assessment of drug effects in a convenient vertebrate model, prior to proceeding to evaluation in complex systems, such as mouse, can potentially streamline drug development and dramatically reduce costs. Zebrafish mutants exhibiting aberrant apoptosis in the central nervous system are an excellent animal model for studying neurodegeneration. Using a zebrafish neurodegenerative mutant line and a vital dye apoptosis assay, this Small Business Innovation Research project proposes to characterize embryogenesis and apoptotic patterning in zebrafish embryos, and to develop a rapid and effective in vivo screen for neuroprotective therapeutics.

描述（由申请人提供）：异常凋亡与几种神经退行性疾病有关，包括中风，脑外伤，脊髓损伤，帕金森氏病，肌萎缩性侧面硬化症（ALS），阿尔茨海默氏症和亨廷顿氏病。这些神经退行性疾病与高发病率和死亡率有关，治疗方案受到限制。调节细胞凋亡的代理是生物制药公司药物开发工作的主要重点。在诸如小鼠等复杂系统中进行评估之前，在方便的脊椎动物模型中评估药物作用可以潜在地简化药物开发并大大降低成本。中枢神经系统中表现出异常凋亡的斑马鱼突变体是研究神经退行性的极好动物模型。这个小型企业创新研究项目使用斑马鱼神经退行性突变系和重要的染料凋亡测定法，建议在斑马鱼胚胎中表征胚胎生成和凋亡模式，并开发一种快速有效的在体内筛查神经治疗疗法的体内筛查。