SELENOPROTEINS AND SYNAPTIC CHANGES IN ALZHEIMERS DISEASE

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 硒蛋白含有微量元素硒(Se)，结合在第21个氨基酸硒半胱氨酸中。硒蛋白P(SelenoProtein P，SELP)具有很强的抗氧化性，能螯合有毒金属。靶向破坏SELP会导致神经功能障碍，包括空间记忆缺陷。我们最近报道了硒蛋白P(SELP)与阿尔茨海默病的病理相关(Bellinger等人，J.阿尔茨海默病，2008)。该项目将研究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合成其他硒蛋白提供硒来保护神经元功能。我们将通过以下目标来验证这一假说：1)通过鉴定与斑块相关的SELP表达细胞，并确定SELP是否可以防止淀粉样蛋白毒性，确定SELP在阿尔茨海默病病理中的作用；2)通过研究SELP缺失小鼠的突触生理学，确定SELP在调节突触变化中的作用；以及3)确定SELP的脑特异性过表达是否改变了突触生理学。这项研究项目将阐明SELP在正常神经功能中的作用，以及它在神经退行性疾病中可能的预防作用。

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.