Stroke, heart attacks and numerous other common disorders result in a massive destruction of cells and tissues called necrosis. It’s a violent event: As each cell dies, its membrane ruptures, releasing substances that trigger inflammation, which in turn can cause more cellular necrosis. A new Weizmann Institute study may help develop targeted therapies for controlling the tissue destruction resulting from inflammation and necrosis.
The study, conducted in the laboratory of Prof. David Wallach of the Biological Chemistry Department, focused on a group of signaling enzymes, including caspase 8, which was discovered by Wallach nearly two decades ago. Earlier studies by scientists in the United States, China and Europe had shown that this group of proteins induces “programmed,” or deliberate, necrosis intended to kill off damaged or infected cells. This revelation had generated the hope that by blocking the induction of necrotic cell death by these proteins, it might be possible to prevent excessive tissue damage in various diseases.
But in the new study, reported in Immunity, Wallach’s team sounds a warning. The researchers have revealed that under conditions favoring inflammation – that is, in the presence of certain bacterial components or other irritants – the same group of signaling enzymes can trigger an entirely different process in certain cells. It can activate a previously unknown cascade of biochemical reactions that causes inflammation more directly, without inducing necrosis, by stimulating the production of hormone-like regulatory proteins called cytokines. The research, mainly based on experiments in transgenic mice lacking caspase 8 in certain immune cells, was spearheaded by postdoctoral fellow Dr. Tae-Bong Kang. Team members Seung-Hoon Yang, Dr. Beata Toth and Dr. Andrew Kovalenko made important contributions to the study.
These findings suggest that prior to developing targeted necrosis-controlling therapies, researchers need to learn more about the signals transmitted by caspase 8 and its molecular partners: Since this signaling can lead to several entirely different outcomes, the scientists need to determine when exactly it results directly in necrosis and when it does not. Clarifying this matter is of enormous importance: Tissue necrosis occurs in a variety of disorders affecting billions of people, from the above-mentioned stroke and heart attack to viral infections and alcoholism-related degeneration of the liver.
Prof. David Wallach’s research is supported by the Leona M. and Harry B. Helmsley Charitable Trust; and Merck Serono. Prof. Wallach is the incumbent of the Joseph and Bessie Feinberg Professorial Chair.
Yivsam Azgad | EurekAlert!
A novel synthetic antibody enables conditional “protein knockdown” in vertebrates
20.08.2018 | Technische Universität Dresden
Climate Impact Research in Hannover: Small Plants against Large Waves
17.08.2018 | Leibniz Universität Hannover
There are currently great hopes for solid-state batteries. They contain no liquid parts that could leak or catch fire. For this reason, they do not require cooling and are considered to be much safer, more reliable, and longer lasting than traditional lithium-ion batteries. Jülich scientists have now introduced a new concept that allows currents up to ten times greater during charging and discharging than previously described in the literature. The improvement was achieved by a “clever” choice of materials with a focus on consistently good compatibility. All components were made from phosphate compounds, which are well matched both chemically and mechanically.
The low current is considered one of the biggest hurdles in the development of solid-state batteries. It is the reason why the batteries take a relatively long...
New design tool automatically creates nanostructure 3D-print templates for user-given colors
Scientists present work at prestigious SIGGRAPH conference
Most of the objects we see are colored by pigments, but using pigments has disadvantages: such colors can fade, industrial pigments are often toxic, and...
Scientists at the University of California, Los Angeles present new research on a curious cosmic phenomenon known as "whistlers" -- very low frequency packets...
Scientists develop first tool to use machine learning methods to compute flow around interactively designable 3D objects. Tool will be presented at this year’s prestigious SIGGRAPH conference.
When engineers or designers want to test the aerodynamic properties of the newly designed shape of a car, airplane, or other object, they would normally model...
Researchers from TU Graz and their industry partners have unveiled a world first: the prototype of a robot-controlled, high-speed combined charging system (CCS) for electric vehicles that enables series charging of cars in various parking positions.
Global demand for electric vehicles is forecast to rise sharply: by 2025, the number of new vehicle registrations is expected to reach 25 million per year....
17.08.2018 | Event News
08.08.2018 | Event News
27.07.2018 | Event News
20.08.2018 | Information Technology
20.08.2018 | Life Sciences
20.08.2018 | Information Technology