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. Alzheimer Disease (AD), the most common form of dementia in the elderly, may manifest as neuropathological changes and cognitive decline long before it is diagnosed. Oxidative stress induced by Reactive Oxygen Species (ROS) has been implicated as a contributing factor to Alzheimer's disease. ROS attack on proteins can lead to protein-bound carbonyl by oxidation of the amino acid side group. Protein carbonyl formation is increased in severely affected regions of the AD brain and may be an early event in the neurodegenerative process. This is considered a marker of oxidative stress in Alzheimer's disease. Therefore, the identification of protein targets of oxidative damage in the AD brain is important. The microfluidic device-proteomic reactor proposed will allow identification of carbonylated proteins from a small sample without the loss of sample that occurs with conventional proteomic methods. Bioinformatics tools will be used to analyze the mass spectrometry data, and obtain quantitative profiling of young vs. old or normal vs. diseased states. Also, Ingenuity Pathway Analysis (IPA), another bioinformatics tool, will facilitate identification of pathways and functions underlying the set of carbonylated proteins that may be differentially affected in the diseased states and with aging. This project aims for a better understanding of major proteins and pathways/functions that may be responsible for aging and age-associated disease. Ultimately, it will help to develop therapeutic approaches to prolong useful life and to treat or prevent diseases.
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