A warning call

New findings by Weizmann Institute of Science scientists will assist in the development of targeted methods to prevent necrosis

Strokes, heart attacks and many other diseases cause extensive destruction of cells and tissues, known as necrosis. This is a violent event: the death of each cell is accompanied by the tearing of the membrane and the spilling out of substances that cause inflammation, as a result of which necrosis of additional cells is caused. New research at the Weizmann Institute of Science may help develop targeted drugs that will prevent tissue destruction resulting from inflammation and necrosis.

The research, carried out in the laboratory of Prof. David Welch from the Department of Biological Chemistry, focused on a group of signal-transmitting enzymes, including the enzyme caspase 8, which Prof. Welch discovered almost two decades ago. Previous studies in the US, China and Europe have shown that this group of proteins leads to "programmed" necrosis, that is, pre-directed, designed to eliminate damaged and infected cells. This discovery gave rise to hope that it will be possible to prevent excessive tissue destruction in various diseases if a way is found to prevent these proteins from leading to necrosis.

But in the new study, which was published in the journal Immunity, the research group of Prof. Welch sounds a warning. The scientists discovered that under conditions that encourage inflammation, that is, in the presence of certain molecules originating from bacteria, or of other molecular threats, the same group of signaling enzymes may lead in certain cells to a completely different process. The enzymes can trigger another chain of biochemical reactions, which was not known before, leading to inflammation in a more direct way, without the necrosis: it encourages the creation of control proteins similar to hormones, called cytokines. The research was mainly based on experiments in genetically engineered mice whose caspase 8 enzyme was missing in certain immune cells. Postdoctoral researcher Dr. Tae-bong Kang made a major contribution to this research. It was also attended by Seung-Hon Ying, Dr. Beata Tut and Dr. Andrew Kovalenko.

The findings indicate that in order to develop targeted treatments to prevent necrosis, scientists need to learn more about the signals transmitted by caspase 8 and the molecular partners of this enzyme. Since these signals may lead to completely different phenomena, the scientists need to understand when exactly the process leads directly to necrosis and when it does not. This distinction is of enormous importance: tissue necrosis occurs in billions of people suffering from many diseases, starting with the strokes and heart attacks mentioned above, and ending with viral infections and liver degeneration as a result of excessive alcohol consumption.

The scientific article: http://www.sciencedirect.com/science/article/pii/S1074761312005146