Stabilizing NOD2 Protein May Provide Effective Therapy For Chron’s Disease

Stabilizing NOD2 Protein May Provide Effective Therapy For Chron’s Disease
NOD2 in Crohn'sHeat shock protein 70’s overexpression stabilizes the Nucleotide-binding oligomerization domain-containing protein 2 (NOD2) Crohn mutants, rescuing its activity and ultimately providing an effective therapy for Crohn’s disease, a study conducted by University of Delaware researchers suggests. The study, published in the Journal of Biological Chemistry and funded by the National Institutes of Health, began by determining the mechanisms of misactivation in the NOD2 Crohn mutants by developing a cell-based system to screen for protein-protein interactors of NOD2. The team identified heat shock protein 70 (HSP70), which has previously been linked to inflammation (especially in the regulation of anti-inflammatory molecules), as a protein interactor of both wild type and Crohn mutant NOD2. As explained in the study, HSP70 assists with the folding of proteins into their correct three-dimensional shapes, even when cells are under stress from elevated body temperatures, such as a fever. Inducing HSP70 expression in cells increased the response of NOD2 to bacterial cell wall fragments. In addition, an HSP70 inhibitor, KNK437, was capable of decreasing NOD2-mediated NF-κB activation in response to bacterial cell wall stimulation. As a result, the team found that HSP70 regulates the half-life of NOD2 by more than four hours, as increasing the HSP70 level in cells increased the h
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