Mutant proteins result in infectious prion disease in miceDecember 08, 2008A worldwide group of scientists has created an infectious prion disease in a mouse model, in a step that may help unravel the mystery of this progressive disease that affects the nervous system in humans and animals. The research team, including Christina J. Sigurdson, D.V.M., Ph.D., assistant professor of pathology at the University of California, San Diego School of Medicine, also discovered that changing the structure of the prion protein by altering just two nucleic acids leads to a fatal neurological disorder in mice. Their findings will be published on line in Proceedings of the National Academy of Sciences (PNAS) the week of December 1. The study, led by Professor Dr. Adriano Aguzzi of the Institute of Neuropathology at the University of Zurich in Switzerland, was designed to investigate the specific changes in the prion protein that may contribute to chronic wasting disease (CWD). CWD is a highly infectious prion disease found in free-ranging deer and elk that is similar to bovine spongiform encephalopathy (BSE, or "mad cow disease") in cattle and Creutzfeldt-Jakob disease in humans. Prion diseases are thought to be a result of a misfolded form of the prion protein that induces formation of amyloid plaques in the brain - changes that are also seen in patients with Alzheimer's disease. By altering two nucleic acids in the prion gene, the researchers developed a transgenic mouse model that expressed the mutant prion protein. These changes resulted in a "loop" in the protein structure of the mice that was rigid - similar to the structure of the elk prion protein, and unlike the flexible "loop" found in normal mouse or human prion proteins. Aging mice with the "rigid loop" prion protein accumulated plaques in the brain and developed symptoms of neurological disease that are features of prion-related disorders. "It could be that this 'loop' region of the protein can promote the formation of amyloid plaques in the brain," said Sigurdson. "We also found that by transferring brain tissue from mice with the mutant protein into mice expressing the normal mouse prion protein, we could transmit the neurologic disease between the two groups of animals." According to Sigurdson, the discovery that an infectious disease can be generated through just two mutations in the prion gene is of particular interest. "Some forms of prion disease in humans caused by genetic mutations have also been shown to be infectious," she said. "This new mouse model of the disease may be useful in our understanding of how the misfolded protein leads to neurodegeneration and for testing new therapies against prion disease." University of California - San Diego |
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| Related Prion Disease Current Events and Prion Disease News Articles Species barrier may protect macaques from chronic wasting disease Data from an ongoing multi-year study suggest that people who consume deer and elk with chronic wasting disease (CWD) may be protected from infection by an inability of the CWD infectious agent to spread to people. Scripps Florida scientists devise accelerated method to determine infectious prion strainsScripps Florida scientists devise accelerated method to determine infectious prion strains Current tests to identify specific strains of infectious prions, which cause a range of transmissible diseases (such as mad cow) in animals and humans, can take anywhere from six months to a year to yield results - a time-lag that may put human populations at risk. Iron is involved in prion disease-associated neuronal demise Imbalance of iron homeostasis is a common feature of prion disease-affected human, mouse, and hamster brains, according to a new study by Dr. Neena Singh and colleagues at Case Western Reserve University School of Medicine, alongside collaborators from Creighton University. Antibody key to treating variant CJD, scientists find Scientists at the University of Liverpool have determined the atomic structure of the 'binding' between a brain protein and an antibody that could be key to treating patients with diseases such as variant CJD. Self-regulating molecular 'transformers' control intracellular protein delivery Scientists from the California Institute of Technology (Caltech) have uncovered the Transformer like properties of molecules responsible for carrying and depositing proteins to their correct locations within cells. Is there more to prion protein than mad cow disease? Prion protein, a form of protein that triggers BSE, is associated with other brain diseases in cattle, raising the possibility of a significant increase in the range of prion disease. K-State professor's USDA research shows mad cow disease also caused by genetic mutation New findings about the causes of mad cow disease show that sometimes it may be genetic. New insights into the diversity of Creutzfeldt-Jakob disease agents Researchers from the United Kingdom and France have identified four separate biochemical subgroups in a selection of cases of Creutzfeldt-Jakob disease. New prion protein discovered by Canadian scientists may offer insight into mad cow disease Scientists have discovered a new protein that may offer fresh insights into brain function in mad cow disease. "Our team has defined a second prion protein called 'Shadoo', that exists in addition to the well-known prion protein called 'PrP' " said Professor David Westaway, director of the Centre for Prions and Protein Folding Diseases at the University of Alberta. Newly discovered antibody may be body's natural defense against Alzheimer's In an important advance in the battle against Alzheimer's disease, physician-scientists at NewYork-Presbyterian Hospital/Weill Cornell Medical Center have identified naturally occurring antibodies in human blood that may help to defend against this form of dementia as well as other neurodegenerative diseases. More Prion Disease Current Events and Prion Disease News Articles |
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