SELENOPROTEINS AND SYNAPTIC CHANGES IN ALZHEIMERS DISEASE

阿尔茨海默病中的硒蛋白和突触变化

• 批准号: 8360705
• 负责人: FREDERICK P BELLINGER
• 金额: $ 6.89万
• 依托单位: UNIVERSITY OF HAWAII AT MANOA
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-06-01 至 2012-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8360705
• 关键词: Alzheimer' s Disease; Amino Acids; Amyloid; Antioxidants; Brain; Cells; Education; Funding; Grant; Hawaii; Knockout Mice; Memory; National Center for Research Resources; Nervous System Physiology; Neurodegenerative Disorders; Neurologic; Neurons; Pathology; Physiology; Principal Investigator; Property; Reporting; Research; Research Infrastructure; Research Project Grants; Resources; Role; Selenium; Selenocysteine; Source; Synapses; Testing; Toxic effect; Trace Elements; United States National Institutes of Health; cost; overexpression; selenoprotein; synaptic function; toxic metal

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Selenoproteins contain the trace element, selenium (Se), incorporated in the 21st amino acid selenocysteine. Selenoprotein P (SelP) has strong antioxidant properties and can chelate toxic metals. Targeted disruption of SelP results in neurological deficits including spatial memory deficiency. We recently reported that selenoprotein P (SelP) is associated with Alzheimer's pathology (Bellinger et al., J. Alzheimers Dis., 2008). This project will investigate the possible neuroprotective role for SelP and determine its importance in synaptic function and memory. We hypothesize that SelP protects neuronal function though direct antioxidant properties as well as supplying selenium for synthesis of other selenoproteins. We will test this hypothesis with the following aims: 1) determine the role of SelP in Alzheimer's pathology by characterizing SelP-expressing cells associated with plaques, and determining if SelP protects against amyloid toxicity, 2) determine the role of SelP in modulating synaptic changes by investigating synaptic physiology in SelP null mice, and 3) determine if brain-specific overexpression of SelP alters synaptic physiology. This research project will clarify the role of SelP in normal neurological function and its possible preventative role in neurodegenerative disorders.

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 硒蛋白含有微量元素硒（Se），其结合在第21位氨基酸硒代半胱氨酸中。硒蛋白P（SelP）具有很强的抗氧化能力，能螯合有毒金属。SelP的靶向破坏导致神经缺陷，包括空间记忆缺陷。我们最近报道了硒蛋白P（SelP）与阿尔茨海默病病理学相关（Bellinger等人，J.阿尔茨海默病，2008年）。本项目将研究SelP可能的神经保护作用，并确定其在突触功能和记忆中的重要性。我们假设SelP通过直接的抗氧化特性以及为其他硒蛋白的合成提供硒来保护神经元功能。我们将测试这一假设与以下目标：1）确定SelP在阿尔茨海默病的病理学的作用，通过表征SelP表达细胞与斑块，并确定是否SelP保护淀粉样蛋白毒性，2）确定SelP在调节突触变化的作用，通过研究突触生理学SelP无效小鼠，和3）确定是否大脑特异性过度表达的SelP改变突触生理学。该研究项目将阐明SelP在正常神经功能中的作用及其在神经退行性疾病中可能的预防作用。