419회 Novel Small Molecule Necrosis Inhibitors as Therapeutic Candidate…

419회 (2008. 10. 23.)

연사: 서 동 욱, LG생명과학

제목: Novel Small Molecule Necrosis Inhibitors as Therapeutic Candidates for Liver Fibrosis/Cirrhosis  

Abstract 

There is extensive evidence that necrotic cell death plays a prominent role in a wide range of human pathological conditions, such as MI, ischemic injury and neurodegeneration. Very little attempt, however, has been made to develop therapeutic agents to specifically target necrosis because of the conventional notion that, unlike apoptosis, necrotic cell death is an unregulated response to stress. The aim of this study is to discover anti-necrotic agents. We identified a novel class of small molecules that inhibited the “necrosis”-specific cell death and their action appears to be different from apoptosis and autophagy as well as necroptosis. These small molecules significantly attenuated the progression of CCl4- or CCl4/EtOH-induced liver fibrosis/cirrhosis in rats (4 weeks). Furthermore, fibrotic/cirrhotic rats (after 8 weeks CCl4 intoxication) treated with these molecules, by 4 weeks more continuation of CCl4, showed significant prevention and reversion of the progression of liver fibrosis/cirrhosis.  These data indicate that necrotic cell death pathway may be critical for the development and relevant in human liver fibrosis/cirrhosis. We suggest that these necrosis inhibitors be as potential therapeutic candidates for necrosis-related disorders such as ischemia, neurodegenerative diseases.