Assistant Professor Toru Okamoto and Professor Yoshiharu Matsuura of the Institute for Microbial Diseases, Osaka University have suppressed the growth of "hepatitis C virus," which is the main cause of viral liver cancer, which accounts for 7% of liver cancer in Japan, and have a liver condition. I found a mechanism to improve.It was confirmed in a mouse model that inhibition of an enzyme called the signal peptide peptidase (SPP) reduces the production of viral particles and improves liver pathology. Helps develop new treatments for hepatitis C.
Among the gamma secretase inhibitors under development as a therapeutic agent for Alzheimer's disease, we found a compound that inhibits SPP.As a result of applying these drugs and gene editing technology, it was discovered that the immature core protein that is not cleaved by SPP is recognized by an enzyme called TRC8 and rapidly degraded.When this degradation pathway is suppressed, cell damage is strongly induced by endoplasmic reticulum stress, which is considered to be a new protein quality control mechanism.In addition, it was confirmed in mice that inhibition of SPP activity significantly reduced hepatitis C virus particle production and improved liver pathology such as insulin resistance and fatty liver.
Approximately 2 million people worldwide are infected with the hepatitis C virus, and when infected with this virus, fatty liver, liver fibrosis, and liver cancer develop.Recently, highly effective drugs targeting viral replication enzymes have been developed and can eliminate hepatitis C virus, but many such as the emergence of resistant viruses and the onset of liver cancer after virus elimination. The problem remains. It was known that the core protein that forms hepatitis C virus particles is cleaved by SPP in infected host cells, which is important for the formation of virus particles and the development of liver pathology, but the details are clear. It wasn't.
