Researchers identify new mechanisms able to suppress the spread of HCV -
Researchers at Osaka University in Japan discovered the mechanisms that suppress the spread of virus hepatitis C (HCV) with the potential to improve the conditions of liver disease. Using model mice, they confirmed that when a certain enzyme is inhibited, the production of HCV particles is reduced leading to an improvement of pathological conditions of the liver. They thus identified a new drug target for the development of new drugs against HCV.
Approximately 0 million people worldwide are infected with HCV virus. HCV infection can cause fatty liver, liver fibrosis and liver cancer. In Japan, the Hepatitis C virus is the leading cause of viral liver cancer, which is 70% of liver cancers. Although the recent development of effective drugs targeting the HCV replicative enzymes has allowed the elimination of HCV, challenges remain including the emergence of resistant viruses and the development of liver cancer after the elimination of the virus. Until now it was known that cleavage of the HCV capsid protein by the enzyme signal peptidase peptide (SPP) in infected host cells have played an important role in virus particle formation and growth conditions pathological liver. However, details of this mechanism are not included.
A research group led by Toru Okamoto, assistant professor and Yoshiharu Matsuura, a professor at the Research Institute for Microbial Diseases, Osaka University has now discovered that when the SPP enzyme inhibition production, HCV particles is reduced resulting in improvement of the pathological liver conditions.
researchers found a chemical compound which inhibits the enzyme in SPP? -secretase Inhibitor that is currently in the process of development for treatment of Alzheimer's disease. They also discovered that immature core protein that are not cleaved by SPP are recognized by the enzyme TRC8 and rapidly degraded. If this degradation process is removed, the cell damage is strongly induced by the stress of the endoplasmic reticulum (ER stress). The endoplasmic reticulum is the heart of the biosynthesis of proteins and in a state of stress of the ER, the protein synthesis, there are unable to fold correctly causing damage to cells. This degradation process can therefore be considered as a quality of the novel proteins control mechanism. When the researchers administered the SPP inhibitor to model mice, the production of HCV particles was significantly reduced, improving HVC pathological conditions such as insulin resistance and fatty liver.
The results of this study suggest that the development of inhibitors of the PSP as a new hepatitis C drug. In addition, the quality control mechanism of a protein observed via the PSP / TRC8 is believed to be related to other diseases can thus potentially useful for the development of drugs for various diseases.
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