Jefferson scientists discover a key protein regulator of inflammation and cell deathJanuary 23, 2009(PHILADELPHIA) Reporting in the journal Nature, researchers led by Emad Alnemri, Ph.D., professor of Biochemistry and Molecular Biology in the Kimmel Cancer Center at Jefferson, discovered a key protein component involved in inflammation. The protein, AIM2 (absent in melanoma 2), is involved in the detection and reaction to dangerous cytoplasmic DNA that is produced by infection with viral or microbial pathogens, or by tissue damage. AIM2 also appears to be a tumor suppressor, and its inactivation may play a role in the development of cancer, according to Dr. Alnemri. AIM2 belongs to a class of proteins called inflammasomes, which are multi-protein complexes that play major roles as guardians against both viral and bacterial infections. Inflammasomes also detect dangerous self-molecules associated with tissue damage. According to Dr. Alnemri, when cells are infected with pathogens, AIM2 senses the presence of the pathogen's DNA in the cytoplasm. It then binds to the foreign DNA and causes a rapid inflammatory reaction that sends a danger signal alerting the body to the invading pathogen. When AIM2 binds to the foreign DNA, it recruits a cytoplasmic protein called ASC. ASC and AIM2 then work together to activate caspase-1, a cysteine protease involved in the production of interleukin1beta and other inflammatory cytokines that cause inflammation. "Researchers have long sought this elusive protein that senses the presence of DNA in the cytoplasm, which is associated with pathogenic infection or the escape of undigested self-DNA into the cytoplasm," Dr. Alnemri said. "We not only identified the key protein in this process, but also discovered how this protein reacts to DNA and causes inflammation. The inflammatory response triggered when AIM2 binds to foreign DNA in the cytoplasm is the body's way of alerting other systems that there is a danger present in the cell." According to Dr. Alnemri, the activation of AIM2 also leads to death of the infected cells, which removes the damaged cells from the body. This prevents the pathogen from replicating in the cells and spreading to other parts of the body. The fact that AIM2 can induce cell death raises the possibility that AIM2 might function as a tumor suppressor, by killing cells with damaged DNA before they transform into cancers. Inactivation of AIM2 thus might confer a growth advantage to abnormal cells and lead to the development of cancer. "The discovery and understanding of the AIM2 inflammasome should enable scientists to design novel therapeutics that modulate its activity," Dr. Alnemri said. "Such therapeutics may be useful for the treatment of nucleic acid-dependent pathogenic and autoimmune diseases, such as arthritis and systemic lupus erythematosus," Dr. Alnemri said. Thomas Jefferson University |
|||||||||||||||||||||
| Related Cell Death Current Events and Cell Death News Articles New understanding about mechanism for cell death after stroke leads to possible therapy Scientists at the Brain Research Centre, a partnership of the University of British Columbia Faculty of Medicine and Vancouver Coastal Health Research Institute, have uncovered new information about the mechanism by which brain cells die following a stroke, as well as a possible way to mitigate that damage. Sweet -- sugared polymer a new weapon against allergies and asthma Scientists at Johns Hopkins and their colleagues have developed sugar-coated polymer strands that selectively kill off cells involved in triggering aggressive allergy and asthma attacks. UAB Researchers Discover Antibody Receptor Identity, Propose Renaming Immune-System Gene Researchers at the University of Alabama at Birmingham (UAB) have uncovered the genetic identity of a cellular receptor for the immune system's first-response antibody, a discovery that sheds new light on infection control and immune disorders. Inhibition of GRK2 is protective against acute cardiac stress injuries Inhibition of a protein known to contribute to heart failure also appears to be protective of the heart in more acute cardiac stress injury, namely ischemia reperfusion. Researchers find potential treatment for Huntington's disease Investigators at Burnham Institute for Medical Research (Burnham), the University of British Columbia's Centre for Molecular Medicine and Therapeutics and the University of California, San Diego have found that normal synaptic activity in nerve cells (the electrical activity in the brain that allows nerve cells to communicate with one another) protects the brain from the misfolded proteins associated with Huntington's disease. Research reveals lipids' unexpected role in triggering death of brain cells The lipid that accumulates in brain cells of individuals with an inherited enzyme disorder also drives the cell death that is a hallmark of the disease, according to new research led by St. Jude Children's Research Hospital investigators. Cornell researchers identify a weak link in cancer cell armor The seeming invincibility of cancerous tumors may be crumbling, thanks to a promising new gene therapy that eliminates the ability of certain cells to repair themselves. Sponges recycle carbon to give life to coral reefs Coral reefs support some of the most diverse ecosystems on the planet, yet they thrive in a marine desert. So how do reefs sustain their thriving populations? Aileron collaborates study in Nature: Stapled peptides inhibit Notch1 transcription factor This research validates the potential for Stapled Peptides to modulate key intracellular biological targets, such as transcription factors, that have not been addressable with current small molecule or biologic drug modalities. CSHL team solves structure of NMDA receptor unit that could be drug target for neurological diseases A team of scientists at Cold Spring Harbor Laboratory (CSHL) reports on Thursday their success in solving the molecular structure of a key portion of a cellular receptor implicated in Alzheimer's, Parkinson's, and other serious illnesses. More Cell Death Current Events and Cell Death News Articles |
|||||||||||||||||||||
|
|||||||||||||||||||||
|
|||||||||||||||||||||