Leading the way to a cure


Immunoproteasome selective inhibitors for lupus treatment

Lin, Gang, PhD

Joan & Sanford I. Weill Medical College of Cornell University

Proteasomes, barrel-shaped protein complexes located within cells, function to break up and clear out proteins that are damaged or no longer useful. Thus, through degradation, the proteasome exerts control over a considerable range of cellular activities. 

Inhibiting all activities of the proteasome would be very harmful to a person. A medicine that inhibits the activities of the proteasome is already being used by cancer patients but this medicine has side effects that make it too toxic for long-term use on a regular basis. However, a medicine targeting a subfamily of the proteasome, called immunoproteasome, that are expressed in immune system in a highly specific way and this selective inhibition might be tolerable for long-term use, as is needed for lupus.

Previously Dr. Lin developed inhibitors that affected the proteasomes of bacteria but did not affect the proteasomes of the humans. Recently, he has developed inhibitors that are highly specific for immunoproteasomes whose action can be reversed. All of these inhibitors are within a class of reversible proteasome inhibitors with the tongue-twisting name of N,C-capped dipeptides. At present, his research is seeking to further characterize these inhibitors and to test them in a mouse model of lupus. 

What this study means for people with lupus: We hope this research will develop these inhibitors or other substances related to them into novel lupus therapies. 

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