Drug used for alcoholism shows potential for stopping inflammatory disease

Could a drug used to treat alcoholism also treat Alzheimer’s? 

A recent University of Michigan study reveals how the drug disulfiram, which blocks the liver’s ability to process alcohol resulting in discomfort and a severe hangover, also shuts down an inflammatory complex known as NLRP3. 

This inflammatory process is suspected to lead to a number of other common diseases, including Alzheimer’s and diabetes.

The discovery was accidental, said lead author Jie Xu, Ph.D., of the Department of Pathology at the University of Michigan Medical School, who works in the laboratory of Gabriel Nuñez, M.D., and was researching drugs that inhibit a protein activated downstream from the NLRP3 inflammasome.

An inflammasome is a type of sensor designed to respond to specific threats and upon activation induces inflammation.

Xu, along with collaborators Nuñez, and Joseph Pickard, Ph.D., found that disulfiram blocks a process called palmitoylation, which adds a lipid onto the NLRP3 protein required to shuttle it within the cell in order to activate it. 

To further support their finding, they stimulated the inflammatory process in mice using a bacterial toxin and found that administering disulfiram reduced NLRP3-mediated inflammation. 

Said Xu, "This FDA-approved drug is considered safe, so it may be repurposed. Alternatively, using new information about its mechanism of action, chemists could develop derivatives that are even more specific to the NLRP3 inflammasome."

Paper cited: “FDA-approved disulfiram inhibits the NLRP3 inflammasome by regulating NLRP3 palmitoylation,” Cell Reports. DOI: 10.1016/j.celrep.2024.114609