Introduction Activated glial cells secrete a variety of proteins includ inhibitor Volasertib ing proinflammatory cytokines, chemokines, Inhibitors,Modulators,Libraries and neuro toxic factors under inflammatory or pathological conditions. Secretomic analysis has been previously conducted for astrocytes and microglia to de termine the profile of the secreted proteins. Some of these secreted proteins play important roles in the pro gression of inflammatory diseases in the brain, and serve as biomarkers that can be used to guide diagnosis and drug therapy. Microglia, the resident macrophages of the CNS, constitute the brains innate immune Inhibitors,Modulators,Libraries system and play a pivotal role in neuroinflammation and host defense against microbial agents. Microglia, as phagocytes, engulf invaded pathogens, apoptotic cells, and their debris.

Inhibitors,Modulators,Libraries Chronically activated microglia also contribute to neurotoxicity in neurodegenerative diseases, such as Alzheimers disease, Parkinsons disease, amyotrophic lateral sclerosis, Huntingtons disease, and multiple sclerosis. Migration of microglia, via extension of their processes, to the site of inflammation is a key step in the progression of the inflammatory brain diseases. Plasminogen activator inhibitor type 1, also known as serine protease inhibitor E1, is expressed in various cell types such as adipocytes, glomerular mesan gial cells, epithelial cells, vascular endothelial cells, vas cular smooth muscle cells, monocytes macrophages, and astrocytes. PAI 1 acts as the main inhibitor of both urokinase type plasminogen activators and tissue type plasminogen activators, which convert plasminogen to plasmin.

This plasmin activator inhibitor system is involved in the regulation of fibrinolysis, and remodeling of the extracellular matrix, cell migration, and invasion of tumor cells. PAI 1 is also involved in the distinction between viable and apoptotic cells, and PAI 1 regulates the phagocytosis of apoptotic cells. PAI 1 plays a dual role in the regulation of cell Inhibitors,Modulators,Libraries migration Inhibitors,Modulators,Libraries through differential interactions with its bind ing partners such as uPA, tPA, vitronectin, and low density lipoprotein receptor related protein 1. The PAI vitronectin complex binds to the Arg Gly Asp motif of v integrins and inhibits the integrin mediated cell migration. The PAI 1 uPA uPAR complex inhibits uPA induced cell migration, whereas the interaction between PAI 1 and LRP1 stimulates the movement of monocytes.

The LRP1 tPA PAI 1 complex induces Mac 1 dependent macrophage migra tion. Thus, the effect of PAI 1 on cell migration depends on the binding proteins involved, which are expressed in a cell and tissue specific manner. Overex pression of PAI 1 has been detected in various brain dis orders, such as glioma, ischemic stroke, MS, and AD. Several example reports have indicated an important role of PAI 1 in the CNS injury and pathology.