THE ROLE OF C/EBPS IN ALZHEIMER'S DISEASE INFLAMMATION

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 斯特罗迈耶斯博士的研究兴趣在于神经退行性疾病中的慢性脑部炎症，主要关注的是慢性炎症在阿尔茨海默病大脑中的作用。神经退行性疾病，如阿尔茨海默病、帕金森氏病和多发性硬化症，其最终有害结果是通过各种不同的过程导致神经元死亡。 慢性脑炎症在阿尔茨海默病的大脑中已经研究了近20年，并导致了对炎性蛋白和有毒分子的广泛研究，以及它们对脑细胞的影响，甚至是产生它们的脑细胞。事实上，斯特罗迈尔博士的研究生涯始于进行这些类型的研究。较少研究的是调节这些过程的细胞内的控制。细胞通过仔细调节编码蛋白质和分子的基因在细胞核DNA中的表达来控制它们的表达。被称为转录因子的特殊蛋白质共同作用，实现了非常严格的基因表达程序。 斯特罗迈耶斯博士目前的研究兴趣是研究一个转录因子家族，该家族在调节阿尔茨海默氏病的几个相关细胞程序方面发挥着核心作用。这个家族被称为CCAAT/增强子结合蛋白(C/EBPs)，有六个成员，用希腊字母(？，？)表示。与其他类型的转录因子一起和结合，C/EBPs有助于调节细胞的能量代谢、细胞增殖和分化以及炎症。虽然所有这些都是阿尔茨海默病研究的重要领域，但斯特罗迈耶博士目前正专注于研究C/EBPs在调节脑内小胶质细胞和星形胶质细胞中炎症基因表达方面的作用。Strohmeyer博士已经证明，这两种脑细胞表达C/EBPs，并有望调节这些细胞中的炎症基因。Strohmeyers博士的研究目标是证明这一点，并确定细胞中必须出现的信号才能激活C/EBPs。通过进行进一步了解这些过程的研究，我们可能获得新的见解，这些见解可能被证明对阿尔茨海默氏症和其他具有炎症成分的神经退行性疾病的治疗有用。 斯特罗迈耶斯博士的研究目前包括以下四个详细目标： 描述了每个C/EBP亚型在人脑组织和脑细胞培养中的表达模式。 评估C/EBPs在调节细胞因子、趋化因子、补体、iNOS和其他炎症基因表达方面的功能。 评估C/EBPs在神经胶质细胞活化和分化中的作用，以响应炎症刺激，如淀粉样蛋白和细胞因子。 确定C/EBPs是否可能受到一种抗炎信号通路的调节，这些信号通路由统称为他汀类药物、非类固醇抗炎药(NSAID)或PPAR-γ激动剂的降胆固醇药物触发。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Dr. Strohmeyers research interests lie in the area of chronic brain inflammation in neurodegenerative diseases, with a primary focus being the role of chronic inflammation in the Alzheimers disease brain. Neurodegenerative diseases, such as Alzheimers disease, Parkinsons disease, and Multiple Sclerosis, are diseases wherein the final detrimental outcome is the death of neurons by a variety of different processes. Chronic brain inflammation has been studied in the Alzheimers disease brain for nearly two decades and has resulted in extensive studies of the inflammatory proteins and toxic molecules, their effects on brain cells, and even the brain cells producing them. Indeed, Dr. Strohmeyer began his research career performing these types of studies. Less well studied have been the controls within cells that regulate these processes. Cells control their expression of proteins and molecules by carefully regulating the expression of the genes encoding them in the DNA of the cells nucleus. Special proteins called transcription factors work together to achieve a very tightly controlled programs of gene expression. Dr. Strohmeyers current research interests are in studying a transcription factor family that plays a central role in regulating several cellular programs of interest in Alzheimers disease. This family is known as the CCAAT/Enhancer Binding Proteins (C/EBPs) and has six members designated with Greek letters (¿, ¿, ¿, ¿, ¿, ¿). Together and in combination with other types of transcription factors, C/EBPs help regulate cellular programs of energy metabolism, cell proliferation and differentiation, and inflammation. Though all are important areas in Alzheimers research, Dr. Strohmeyer is currently focusing on studying the role of C/EBPs in regulating the expression of inflammatory genes in microglia and astrocyte cells in the brain. These two brain cell types have been shown to express C/EBPs by Dr. Strohmeyer and are expected to regulate inflammatory genes in these cells. Dr. Strohmeyers research objective is to show this to be the case and to determine the signals that must occur in the cell to activate C/EBPs. By conducting studies that further our understanding of these processes, we may obtain novel insights that might prove to be therapeutically useful in Alzheimers and other neurodegenerative diseases having an inflammatory component. Dr. Strohmeyers research currently encompasses the following four detailed objectives: " Characterizing the expression pattern of each C/EBP isoform in human brain tissue and in brain cell cultures. " Assessing the functionality of C/EBPs in modulating the expression of cytokine, chemokine, complement, iNOS, and other inflammatory genes. " Assessing the role of C/EBPs in glial cell activation and differentiation in response to inflammatory stimuli such as ¿-amyloid protein and cytokines. " Determining whether C/EBPs may be modulated by an anti-inflammatory signaling pathways triggered by cholesterol-lowering drugs collectively known as statins, non-steroidal anti-inflammatory drugs (NSAIDs), or PPAR-gamma agonists.