Huntington's disease is one of a number of degenerative diseases marked by clumps of malformed protein in brain cells. Symptoms include abnormal movements, psychiatric disturbances like depression and a form of dementia. The gene responsible for the disease was discovered in 1993, leading to a better understanding of the condition and to improved predictive genetic testing, but it has yet to lead to any treatments that slow the neurodegeneration in Huntington's patients.
Professor David Rubinsztein, a Wellcome Trust Senior Clinical Fellow at the University of Cambridge, has been studying the molecular biology underlying Huntington's and other neurodegenerative diseases. Huntington's occurs when a protein known as huntingtin builds up in the brain cells of patients, mainly in neurons in the basal ganglia and in the cerebral cortex. Normally, cells dispose of or recycle their waste material, including unwanted or mis-folded proteins, through a process known as autophagy, or "self-eating".
"We have shown that stimulating autophagy in the cells – in other words, encouraging the cells to eat the malformed huntingtin proteins – can be an effective way of preventing them from building up," says Professor Rubinsztein. "This appears to stall the onset of Huntington's-like symptoms in fruit fly and mice, and we hope it will do the same in humans."
Autophagy can be induced in mouse and fly models by administering the drug rapamycin, an antibiotic used as an immunosuppressant for transplant patients. However, administered over the long term, the drug has some side effects and Rubinsztein and colleagues are aiming to find safer ways of inducing autophagy long term.
Now, Professor Rubinsztein, together with Professor Stuart Schreiber’s lab at the Broad Institute of Harvard/MIT, Boston in the US, and Dr Cahir O’Kane’s group in the Department of Genetics at the University of Cambridge have found a way of identifying novel "small molecules" capable of inducing autophagy. The research is published today in the journal Nature Chemical Biology.
The screening process involves identifying small molecules that enhance or suppress the ability of rapamycin to slow the growth of yeast, though the selected molecules have no effects on yeast growth by themselves. Yeast is a single-celled organism and therefore less complex to study for initial screening purposes.
Three of the molecules that enhanced the growth-suppressing effects of rapamycin in yeast were also found to induce autophagy by themselves in mammalian cells independent of the action of rapamycin. These molecules enhanced the ability of the cells to dispose of mutant huntingtin in cell and fruit fly models and protect against its toxic effects.
"These compounds appear to be promising candidates for drug development," says Professor Rubinsztein. "However, even if one of the candidates does prove to be successful, it will be a number of years off becoming available as a treatment. In order for such drugs to be useful candidates in humans, we will need to be able to get them into right places in the right concentrations, and with minimal toxicity. These are some of the issues we need to look at now."
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Nanoparticles help with malaria diagnosis – new rapid test in development
21.11.2017 | Fraunhofer-Institut für Silicatforschung ISC
The WHO reports an estimated 429,000 malaria deaths each year. The disease mostly affects tropical and subtropical regions and in particular the African continent. The Fraunhofer Institute for Silicate Research ISC teamed up with the Fraunhofer Institute for Molecular Biology and Applied Ecology IME and the Institute of Tropical Medicine at the University of Tübingen for a new test method to detect malaria parasites in blood. The idea of the research project “NanoFRET” is to develop a highly sensitive and reliable rapid diagnostic test so that patient treatment can begin as early as possible.
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The formation of stars in distant galaxies is still largely unexplored. For the first time, astron-omers at the University of Geneva have now been able to closely observe a star system six billion light-years away. In doing so, they are confirming earlier simulations made by the University of Zurich. One special effect is made possible by the multiple reflections of images that run through the cosmos like a snake.
Today, astronomers have a pretty accurate idea of how stars were formed in the recent cosmic past. But do these laws also apply to older galaxies? For around a...
Just because someone is smart and well-motivated doesn't mean he or she can learn the visual skills needed to excel at tasks like matching fingerprints, interpreting medical X-rays, keeping track of aircraft on radar displays or forensic face matching.
That is the implication of a new study which shows for the first time that there is a broad range of differences in people's visual ability and that these...
Computer Tomography (CT) is a standard procedure in hospitals, but so far, the technology has not been suitable for imaging extremely small objects. In PNAS, a team from the Technical University of Munich (TUM) describes a Nano-CT device that creates three-dimensional x-ray images at resolutions up to 100 nanometers. The first test application: Together with colleagues from the University of Kassel and Helmholtz-Zentrum Geesthacht the researchers analyzed the locomotory system of a velvet worm.
During a CT analysis, the object under investigation is x-rayed and a detector measures the respective amount of radiation absorbed from various angles....
The quantum world is fragile; error correction codes are needed to protect the information stored in a quantum object from the deteriorating effects of noise. Quantum physicists in Innsbruck have developed a protocol to pass quantum information between differently encoded building blocks of a future quantum computer, such as processors and memories. Scientists may use this protocol in the future to build a data bus for quantum computers. The researchers have published their work in the journal Nature Communications.
Future quantum computers will be able to solve problems where conventional computers fail today. We are still far away from any large-scale implementation,...
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