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Archive - Oct 30, 2011

Fragile X Protein Plays Key Role in RNA Editing

The most common form of heritable cognitive impairment is Fragile X syndrome, caused by mutation or malfunction of the FMR1 gene. Loss of FMR1 function is also the most common genetic cause of autism. Understanding how this gene works is vital to finding new treatments to help Fragile X patients and others. Researchers from the Perelman School of Medicine at the University of Pennsylvania, and colleagues from Brown University, have identified the FMRP protein (encoded by FMR1) as a key player in RNA editing, a process in which the working copies made from DNA, called messenger RNAs, are chemically altered after being transcribed from the genome. The scientists’ findings were published online on October 30, 2011 in Nature Neuroscience. Because RNAs are used as the instructions to make proteins, mistakes in RNA editing at the neuromuscular junction (NMJ), the site at which motor neurons innervate muscle, may cause problems in nerve function. Previous work at Penn and several other institutions strongly suggested the role of FMRP to be in regulating the translation of certain types of RNA at the synapse, the space between two nerves, or between nerves and muscles. "Most of the field has been focused on looking at FMRP interacting with specific RNAs and how it regulates their translation at the synapse," states lead author Dr. Thomas A. Jongens, associate professor of genetics at Penn. "Here we've tapped into identifying a function that FMRP has in regulating another process called RNA editing that is important in regulating neural activity." In RNA editing, the information encoded by DNA into an RNA molecule is altered, thus affecting the functioning of the proteins encoded by that RNA.

Scientists ID Misfolded Protein Form That Best Predicts Neuron Death in Huntington’s Disease

Scientists at the Gladstone Institutes in San Francisco, California, have discovered how a form of the protein linked to Huntington's disease influences the timing and severity of its symptoms, offering new avenues for treating not only this disease, but also a variety of similar conditions. In a paper published online on October 30, 2011 in Nature Chemical Biology, the laboratory of Gladstone Senior Investigator Dr. Steven Finkbeiner singles out one form of a misfolded protein in neurons that best predicts whether the neuron will die. Neuronal death is key to the development of Huntington's symptoms—including erratic behavior, memory loss, and involuntary muscle movement. This research underscores the value of the cross-disciplinary work done at Gladstone—a leading and independent biomedical–research organization—while revealing techniques that scientists anywhere can apply to conditions involving misfolded proteins, such as Alzheimer's disease and type 1 diabetes. "Effective treatments for diseases such as Huntington's and Alzheimer's have been slow to develop," said Dr. Finkbeiner, whose research at Gladstone investigates the interactions between genes, neurons, and memory. "We hope that our newfound understanding of precisely which misfolded proteins contribute to disease symptoms will speed up drug development for sufferers." Huntington's, an ultimately fatal disease that affects more than a quarter of a million people nationwide, is caused by mutations in the gene that creates the huntingtin, or htt, protein. As the mutated gene produces htt, a segment of the protein called polyglutamine is mistakenly expanded, distorting htt's natural shape and function. As a result, the misfolded protein malfunctions and can be toxic.

New Malaria Vaccine Addresses Different Forms of the Disease

A new malaria vaccine could be the first to tackle different forms of the disease and help those most vulnerable to infection, a study suggests. The new vaccine is designed to trigger production of a range of antibodies to fight the many different types of parasite causing the disease. Scientists created the vaccine by combining multiple versions of a key protein found in many types of malaria parasite, which is known to trigger production of antibodies upon infection. Mixing multiple proteins from various parasite types induces antibodies against a wide range of the parasites causing the disease. Researchers from the University of Edinburgh, who developed the vaccine, say that because malaria parasites exist in many forms, the only way to gain natural immunity against all strains is by having multiple bouts of the illness. A vaccine that overcomes this could be especially useful in children and other vulnerable groups of people. Many previous vaccines against malaria have had limited success because they target only a limited part of the parasite population. The new vaccine has also been shown to be effective in animals. Tests in blood samples from children in endemic areas showed that the antibodies against this key protein offered improved protection against the disease. Scientists now hope to carry out full-scale human trials. Malaria is spread by mosquito bites and affects people and animals, mostly in sub-Saharan Africa. According to the World Health Organization, in 2009 the disease affected 225 million people and caused an estimated 781,000 deaths, mostly among African children. The new study, published on October 26, 2011 in PLoS ONE, was supported by the European Commission.