Team:Nanjing high school/Description


Project Description
1. Why do we want to do this project?
        Inflammatory neurodegeneration is neuronal death/loss caused by inflammation and is a process (like energy depletion, protein aggregation, and excitotoxicity) contributing to neuronal loss or dysfunction in many different neurological diseases. Many severe degenerative diseases are connected to the inflammatory reaction in our brain. For example, Alzheimer's Disease, Amyotrophic Laternal Sclerosis, and stroke. These diseases are very terrible, they can only be prevented and delayed, but not cured. there is evidence that blocking inflammation can either delay onset or reduce symptoms. Through this project, our goal is to find a compound that may inhibit the inflammatory response in the brain. Meanwhile, we hope that our project will raise more people’s awareness to these diseases.
2. The theory of the project
        Microglia is a type of resident immune cell that balances inflammatory function parts of the brain. But once they become overly inflammatory, they would differentiate into dendritic cells, which in turn may affect many other cells in the brain. This would cause apoptosis injury of other cells and interfere with the balance of microenvironment in the brain.
        Once the microglia are activated, they secrete pro-inflammatory cytokines, including TNFα, IL-1β, and IL-6. Most of the expression changes are a result of activation of the transcription factor NF-κB via phosphorylation-induced activation of IκB kinase. Notably, PPM1A activation could inhibit inflammatory response in peripheral macrophages, and directly dephosphorylate RelA subunit at residues S536 and S276, which is necessary for transcriptional competence of NF-κB.
3. What do we want to get from the project
        Based on the above, we expressed and purified the recombinant human PPM1A protein, and constructed a PPM1A enzyme activity screening platform for screening out PPM1A agonists from FDA-approved drugs library. In this experiment, starting with culturing PPM1A protein, the purified protein was subjected to enzyme activity experiment to evaluate the activation efficiency of the compound, then BV-2 cells (mouse microglia cell line) were cultured, and finally quantitative PCR (Q-PCR) experiment was performed to detect the transcription level of the inflammatory factor, which was calculated to determine the effectiveness of the lead compound, and finally an effective lead compound that can be used for follow-up research is obtained.
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