Targeting G protein-coupled receptors for the treatment of autoimmune diseases

摘要

Our group is interested in the biological functions of G protein-coupled receptor (GPCR) and their roles in major diseases including autoimmune disease, neurodegenerative diseases, metabolic diseases, etc. In addition to the mechanism study, we also screen and develop drugs targeting GPCRs. In recent years, we also seek to study the mechanism of fate determination of stem cells with small molecule compounds. One of the autoimmune diseases we're particularly interested is Multiple Sclerosis (MS). MS is an inflammatory disease that is characterized by immune-mediated demyelin?ation and degeneration of the central nervous system. In the past few years, we've discovered that two GPCRs (CysLT1 and A2B) are critically involved in the development of MS by regulating the differentia?tion or function of immune cells. Blocking these receptors alleviates clinical symptoms of EAE, a mouse model of MS, indicating these receptors are potential drug targets for MS. Current drugs for MS all targets immune system. Although effective in reducing the relapse rate and the formation of new lesions, these drugs have very limited effects in preventing the progression of disability. Promoting oligodendrocyte progenitor cell differentiation, remyelination and subsequent functional recovery of the neurons have been proposed to be the new direction of MS therapy. Our recent study demonstrated that KOR, an opioid receptor, is important for oligodendrocyte-mediated remyelination in EAE, suggesting KOR might be a target to develop new MS therapies from a regenerative point of view.