Proteasome inhibitor clioquinol as a candidate drug in prophylaxis and treatment of acute graft-versus-host disease

摘要: Graft-versus-host disease (GVHD) is one of the most severe complications after allogeneic bone marrow transplantation. It exhibits a complex pathophysiology resulting from donor T cell recognition genetically disparate recipient that unable to reject cells following hematopoietic stem-cell transplantation (HSCT) and ultimately causes multiple organs destruction. Currently practiced prophylaxis GVHD includes T-cell depletion (TCD) and/or immunosuppressive medication. However, agents may have serious side effects selective removal graft significantly reduces beneficial cells, especially anti-tumor activity. These deleterious infectious relapse underlying malignancy remain barriers successful approaches. The proteasomal pathway protein degradation plays key role in different functions such as cycle regulation, apoptosis costimulation. Proteasome inhibition cancer leads induction tumor death also critical roles activation, proliferation, apoptosis, part, because blockade NF-κB activation. Recently it was reported clioquinol can inhibit chymotrypsin-like activity induce apoptotic leukemia myeloma. We hypothesized proteasome inhibitor could be candidate drug for pharmacological treatment with retention graft-versus-tumor (GVT) effect.