The search for monomer-interaction-based alternative TNF-α therapies

Inflammation is regulated by tumor necrosis factor alpha (TNF-α), which as such plays a major role in various autoimmune disorders. High levels of TNF-α induce a wide range of inflammatory phenotypes according to the autoimmune disease in question. Regulating the amount of TNF-α in the body is one of the main treatments administered in order to help alleviate the inflammation that ensues in such conditions. The two autoimmune diseases which will be considered here are psoriasis and rheumatoid arthritis in the contexts of pregnancy and old age. These are particularly sensitive situations as the flare up or development of new inflammatory conditions in these contexts could be associated with serious complications since there are limited treatment options available on the market. Inflammation is elicited by a cascade resulting from the binding of active TNF-α, which is a trimer, to the TNF-α receptor. Most available TNF-α therapies address receptor-binding rather than the TNF-α molecule production or multimerization. The formation of the TNF-α trimer also includes posttranslational modifications but very few have been identified so far, and hence their link to human disease is not characterized. Understanding the trigger, production, assembly, and binding of TNF-α would allow the development of allosteric TNF-α inhibitors to be used in complicated contexts including during pregnancy and old age.