Elasmobranch Fish Model of Neurodegenerative Disease

神经退行性疾病的板鳃鱼模型

• 批准号: 7407612
• 负责人: Jai Dwivedi
• 金额: $ 12.79万
• 依托单位: MARINE BIOMEDICAL TECHNOLOGIES, INC.
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-03-05 至 2008-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7407612
• 关键词: Aging; Alzheimer' s Disease; Animal Model; Animals; Antioxidants; Aquaculture; Biochemical; Biological Markers; Biological Models; Biomedical Technology; Brain; Brain Diseases; Breeding; Cell Line; Cells; Defense Mechanisms; Dementia; Development; Disease; Drug Delivery Systems; Economics; Elasmobranchii; Enzymes; Fishes; Free Radicals; Generations; Genetic; Goals; Housing; Human; Individual; Industry; Laboratories; Mammals; Marines; Metabolic Pathway; Modeling; Modification; Nerve Degeneration; Neurodegenerative Disorders; Neuropathogenesis; Parkinson Disease; Pathogenesis; Pharmacologic Substance; Phase; Population; Preclinical Drug Evaluation; Predisposition; Pregnancy; Risk; Role; Sales; Scientist; Screening procedure; Services; Shark; Study models; System; Therapeutic; Toxic Environmental Substances; Vertebrates; Work; Xenobiotics; cost; cost effective; dopaminergic neuron; drug discovery; enzyme deficiency; human disease; in vivo; insight; pre-clinical; stingray

DESCRIPTION (provided by applicant): Marine Biomedical Technologies plans to develop proprietary elasmobranch fish models of human disease for preclinical drug discovery. We have established that elasmobranch fish demonstrate relevance to human disease and the potential to provide a more accessible, cost effective alternative to other vertebrate models used for analyzing neuropathogenesis. MBT has identified common biomarkers, morphological alterations, and biochemical changes which accompany both Alzheimer's disease (AD) and Parkinson's disease (PD) in humans, in our elasmobranch models. This elasmobranch model also conforms to current models with regard to 1-methyl 4-phenyl 1,2,3,6-tetrahydropyridine (MPTP) induced loss of dopaminergic neurons as seen in human PD. The MBT elasmobranch model offers greater sensitivity to xenobiotic and environmentally induced pathogenesis due to the naturally occurring reduced antioxidant defense capacity as compared to other vertebrates. Our first goal is to establish a breeding population of the species Urolophus jamaicensis (yellow stingray). This species of stingray is readily acclimated to captive breeding, and has the shortest gestation period of elasmobranch fishes. In addition, this species has a large brain to body ratio making it an ideal model for the study of environmentally induced neurodegenerative disease. These stingrays have many systems and homologous metabolic pathways to higher vertebrates, including mammals. These animals can be cultured in relatively little space, at minimal cost, and have a naturally diminished antioxidant defense mechanism without genetic modification, adding to the economic benefits of this model. It is our strong commitment to offer efficient and cost effective therapeutic drug screening services to large pharmaceutical companies as well as individual scientists from both industry and academic settings.Project Narrative Marine Biomedical Technologies Inc. (MBT) is in development of an elasmobranch fish model to directly study the effects of environmental toxicants and their role in neurodegenerative disorders including Parkinson's and Alzheimer's disease. MBT will establish an aquaculture facility to breed stingrays; these animals and cell lines generated will significantly aid in identifying new drug targets for the treatment of degenerative brain disorders. It is our strong commitment to offer efficient and cost effective therapeutic drug screening services to pharmaceutical companies as well as individual scientists from both industry and academic settings.

描述（由申请人提供）：海洋生物医学技术公司计划开发人类疾病的专有板鳃鱼类模型，用于临床前药物发现。我们已经确定，板鳃鱼类表现出与人类疾病的相关性，并有可能提供一个更容易，成本效益的替代其他脊椎动物模型用于分析神经发病机制。MBT已经在我们的板鳃类动物模型中确定了伴随人类阿尔茨海默病（AD）和帕金森病（PD）的常见生物标志物、形态学改变和生化变化。该板鳃类动物模型也符合关于1-甲基4-苯基1，2，3，6-四氢吡啶（MPTP）诱导的多巴胺能神经元损失的当前模型，如在人PD中所见。与其他脊椎动物相比，MBT板鳃类动物模型由于天然存在的抗氧化防御能力降低而对外源性和环境诱导的发病机制具有更高的敏感性。我们的第一个目标是建立一个繁殖种群的物种Urolophus jamaicensis（黄貂鱼）。这种黄貂鱼很容易适应圈养繁殖，并具有最短的妊娠期板鳃类鱼类。此外，该物种具有较大的脑体比，使其成为研究环境诱导的神经退行性疾病的理想模型。这些黄貂鱼有许多系统和同源的代谢途径高等脊椎动物，包括哺乳动物。 这些动物可以在相对较小的空间内以最低的成本培养，并且在没有遗传修饰的情况下具有自然减少的抗氧化防御机制，从而增加了这种模式的经济效益。我们致力于为大型制药公司以及来自工业和学术界的科学家提供高效和具有成本效益的治疗药物筛选服务。项目叙述海洋生物医学技术公司(MBT)正在开发一种板鳃类鱼类模型，以直接研究环境毒物的影响及其在神经退行性疾病（包括帕金森氏症和阿尔茨海默氏症）中的作用。MBT将建立一个养殖黄貂鱼的水产养殖设施;这些动物和产生的细胞系将大大有助于确定治疗退行性脑疾病的新药靶点。我们致力于为制药公司以及来自工业和学术界的科学家提供高效和具有成本效益的治疗药物筛选服务。