The Role of C/EBPS in Alzheimer's Disease Inflammation
This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.Dr. Strohmeyer's 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 Alzheimer's disease brain. Neurodegenerative diseases, such as Alzheimer's disease, Parkinson's 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 Alzheimer's 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. Strohmeyer's current research interests are in studying a transcription factor family that plays a central role in regulating several cellular programs of interest in Alzheimer's 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 Alzheimer's 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. Strohmeyer's 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 Alzheimer's and other neurodegenerative diseases having an inflammatory component.Dr. Strohmeyer's 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.