Prioritization of Therapeutic Targets of Inflammation Using Proteomics, Bioinformatics, and In Silico Cell-Cell Interactomics

Methods in Molecular Biology
Arsalan S Haqqani, Danica B Stanimirovic

Abstract

Protein-protein interactions play key roles in leukocyte extravasation process into the brain and have been attractive therapeutic targets for inhibiting brain inflammation using blocking (or neutralizing) antibodies. These targets include protein-protein interactions between cytokines (or chemokines) and their receptors on leukocytes and between adhesion molecules of leukocyte and brain endothelium. While a number of therapeutics against these targets are currently used in clinic for treatment of brain autoimmune and inflammatory disorders (e.g., multiple sclerosis), they are associated with side effects partly due to the off-target actions (i.e., nonspecific targets). There is a need for novel targets involved in the leukocyte extravasation process that are specific to leukocyte subsets or to individual inflammatory disorder and are amenable for drug development (i.e., druggable). We recently described the blood-brain barrier (BBB) Carta Project as a comprehensive collection of molecular "maps" consisting of multiple experimental omics (including RNA sequencing, proteomics, glycoproteomics, glycomics, metabolomics) and in silico informatics analyses on a number of mammalian species from hundreds of internal, publically availa...Continue Reading

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