FUNCTION OF AN ALZHEIMER DISEASE-RELATED PROTEIN

描述：（改编自申请人的摘要）：本发明的目标是 一项提案是确定神经元蛋白synelfin的正常功能 在成年脊椎动物的端脑中大量存在。 Synelfin已被 从包括人类在内的几个物种中独立分离出来， 被称为NACP（非淀粉样β组分前体）， 表明其与最近从淀粉样蛋白中纯化新肽的关系 阿尔茨海默病（AD）中的斑块。 对鸣禽的研究表明， 高度保守的蛋白质在正常细胞中具有特异性但尚未确定的作用， 突触可塑性的调节。 为了深入了解正常功能 提出了三个研究目标：1）进行生物化学研究， 研究来检验synelfin具有功能关系的假设， 载脂蛋白，如保守的结构观察所示， 功能. synelfin蛋白的正常和突变形式将在细胞中表达。 大肠杆菌，并分析其与磷脂的相互作用，使用 载脂蛋白的良好表征的行为作为比较点。 2)确定蛋白质中负责其 在突触前末梢积累。 突变的DNA构建体将被 导入原代培养的海马神经元， 蛋白质将通过免疫荧光定位。 这些研究可能会给 深入了解蛋白质的表观模块结构，并帮助 实验设计以鉴定与synelfin 互动。 3)在转基因小鼠中过表达synelfin蛋白并测定其作用 关于神经解剖学和神经功能。 这将检验假设 是否synelfin的组成性增加将促进发展， 阿尔茨海默病样神经病理学，或改变发育或行为 依赖于神经可塑性的过程。

DESCRIPTION: (Adapted from Applicant's Abstract): The goal of this proposal is to determine the normal function of synelfin, a neuronal protein abundant in the adult vertebrate telencephalon. Synelfin has been independently isolated from several species, including humans, where it has been referred to as NACP (the Non-Amyloid beta-Component Precursor) to indicate its relationship to a novel peptide recently purified from amyloid plaques in Alzheimer Disease (AD). Studies in songbirds suggest that this highly-conserved protein has a specific but yet-undefined role in the normal regulation of synaptic plasticity. To gain insight into the normal function of synelfin, three research aims are proposed: 1) conduct biochemical studies to test the hypothesis that synelfin has a functional relationship to apolipoproteins, as suggested by observation of conserved structural features. Normal and mutated forms of synelfin protein will be expressed in E.coli and analyzed for their interactions with phospholipids, using the well-characterized behavior of apoliopoproteins as a point of comparison. 2) determine the structural elements in the protein responsible for its accumulation at presynaptic terminals. Mutated DNA constructs will be introduced into primary cultured hippocampal neurons, and the encoded proteins will be localized by immunofluorescence. These studies may give insight into the apparent modular structure of the protein, and help in the design of experiments to identify other proteins with which synelfin interacts. 3) overexpress the synelfin protein in transgenic mice and assay the effect on neuroanatomy and neurological function. This will test the hypothesis whether a constitutive increase in synelfin will promote the development of Alzheimer-like neuropathology, or alter developmental or behavioral processes that depend upon neural plasticity.