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Archive - Mar 8, 2016


Mice Older Than Four Months Do Not Appear to Need the Huntingtin Gene

Adult mice don't need the gene that, when mutated in humans, causes the inherited neurodegenerative disorder Huntington's disease. The finding suggests that treatment strategies for Huntington's that aim to shut off the huntingtin gene in adults -- now in early clinical stages -- could be safe. The results were published online on Monday, March 7, 2016 in PNAS. The article is titled “Ablation of Huntingtin in Adult Neurons Is Nondeleterious But Its Depletion in Young Mice Causes Acute Pancreatitis.” Huntington's disease is caused by a gene encoding a toxic protein (mutant huntingtin) that causes brain cells to die. Symptoms commonly appear in mid-life and include uncontrolled movements, balance problems, mood swings and cognitive decline. A juvenile form of Huntington's disease also can appear during the teenage years. Researchers led by Xiao-Jiang Li, M.D., Ph.D., and Shihua Li, M.D., at Emory University School of Medicine, used genetically engineered mice in which the huntingtin gene can be deleted, triggered only when the mice are given the drug tamoxifen. When the huntingtin gene is deleted at an age older than four months, these mice appeared to stay healthy, despite having lost their huntingtin genes in cells all over their bodies. They maintained their body weight and could complete tests of movement and grip strength as well as control mice. In contrast with adults, engineered mice younger than four months old whose huntingtin gene was deleted developed lethal pancreatitis. The huntingtin gene encodes a large scaffold protein, with many interaction partners, which is thought to be involved in intracellular trafficking. The huntingtin gene is essential for embryonic development, and scientists have already shown that if mouse embryos don't have it at conception, they die in utero.

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New Drug Class Shows Promise Against Legionnaire’s Disease

A new class of drugs has shown promise for treating the bacteria that cause legionnaires' disease, a potentially fatal lung infection. The discovery that “BH3-mimetic” drugs obliterate cells infected with Legionella bacteria could lead to new treatments for a variety of bacterial infections, even those that are resistant to antibiotics. A research team including Dr. James Vince of the Walter and Eliza Hall Institute in Australia, and Dr. Thomas Naderer and Ph.D. student Ms Mary Spier from the Monash University Biomedicine Discovery Institute, also in Australia, showed for the first time that a protein called BCL-XL is an Achilles' heel of Legionella-infected cells. Turning off BCL-XL with BH3-mimetic drugs killed the infected cells, allowing the infection to be cleared from the body. The research was published in the March 2016 edition of Nature Microbiology. The article is titled “Eliminating Legionella by Inhibiting BCL-XL to Induce Macrophage Apoptosis.” People become infected with Legionella bacteria by inhaling contaminated water droplets, often from cooling towers or spas, or contaminated soil such as potting mix. The bacteria hide within human cells called macrophages, escaping the body's own immune defenses and being shielded from many types of antibiotics. People with a weakened immune system, including the elderly, are at particular risk of the serious lung Legionella infection called legionnaires' disease. Dr. Vince said that soon after infecting a macrophage, Legionella bacteria alter the composition of proteins within their host cell to prevent the host from detecting the infection. "We were particularly interested that this drained the macrophage of a protein called MCL-1, that helps to keep cells alive," he said.

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