Huntington’s disease occurs in patients who inherit a mutant form of a protein called Huntingtin (Htt). The protein was first identified in 1993, but how it leads to disease is still poorly understood. One paradox is that the Htt protein is present throughout the body, yet the damage it causes is largely concentrated within specific populations of neurons in the striatum – a brain region also implicated in Parkinson’s disease and other disorders.
The MIT team led by Ann Graybiel, an Institute Professor and member of the McGovern Institute for Brain Research, focused on a gene known as CalDAG-GEFI, which is particularly enriched in the striatal neurons that die in Huntington’s disease. The MIT team showed that CalDAG-GEFI is dramatically down-regulated in the brains of individuals with Huntington’s disease as well as in mouse models of the disease. By following mutant mice for up to 9 months, the researchers showed that this reduction occurs gradually, in parallel with the progression of the disease.
These progressive changes suggest that CalDAG-GEFI is likely to play some role in the disease process. The researchers wanted to determine whether the suppression of this gene is part of the death process, or whether it represents part of the brain’s protective response. They found that the latter explanation appears to be true – when the researchers artificially blocked the expression of CalDAG-GEFI (using a method known as siRNA), the striatal neurons were protected from Htt –induced damage.
“So the enriched expression of CalDAG-GEFI in the striatum may explain, in part, why striatal neurons are particularly vulnerable to the expression of mutant Htt,” explained first author and research scientist, Jill Crittenden of the McGovern Institute for Brain Research. “Switching off of the CalDAG-GEFI gene may represent the neuron’s attempt, ultimately unsuccessful, to save itself.”
Huntington’s disease is currently incurable, and existing treatments address only the symptoms, and have no effect on the course of the disease or its eventual fatal outcome. The researchers hope that by understanding the molecular pathway by which neurons are killed, their findings may suggest new strategies for the development of treatments that could slow or even prevent the progression of the disease.
Source: Crittenden J, Dunn DE, Merali FI, Woodman B, Yim M, Borkowska AE, Frosch MP, Bates GP,Housman DE, Lo DC, Graybiel AM. CalDAG-GEFI Down-regulation in the striatum as a neuroprotective change in Huntington’s Disease. Human Molecular Genetics. 10 February 2010.
Funding: Institute of Child Health and Development, James W. and Patricia T. Poitras Major Mental Illness Research Fund, National Institutes of Mental Health, Wellcome Trust, Cure Huntington’s Disease Initiative, Inc., Hereditary Disease Foundation, Neuropathology Cores of the Massachusetts Alzheimer Disease Research Center, MGH/MIT Morris Udall Center of Excellence in Parkinson Disease Research, and the McGovern Institute for Brain Research at MITJen Hirsch
Jen Hirsch | Newswise Science News
How brains surrender to sleep
23.06.2017 | IMP - Forschungsinstitut für Molekulare Pathologie GmbH
A new technique isolates neuronal activity during memory consolidation
22.06.2017 | Spanish National Research Council (CSIC)
An international team of scientists has proposed a new multi-disciplinary approach in which an array of new technologies will allow us to map biodiversity and the risks that wildlife is facing at the scale of whole landscapes. The findings are published in Nature Ecology and Evolution. This international research is led by the Kunming Institute of Zoology from China, University of East Anglia, University of Leicester and the Leibniz Institute for Zoo and Wildlife Research.
Using a combination of satellite and ground data, the team proposes that it is now possible to map biodiversity with an accuracy that has not been previously...
Heatwaves in the Arctic, longer periods of vegetation in Europe, severe floods in West Africa – starting in 2021, scientists want to explore the emissions of the greenhouse gas methane with the German-French satellite MERLIN. This is made possible by a new robust laser system of the Fraunhofer Institute for Laser Technology ILT in Aachen, which achieves unprecedented measurement accuracy.
Methane is primarily the result of the decomposition of organic matter. The gas has a 25 times greater warming potential than carbon dioxide, but is not as...
Hydrogen is regarded as the energy source of the future: It is produced with solar power and can be used to generate heat and electricity in fuel cells. Empa researchers have now succeeded in decoding the movement of hydrogen ions in crystals – a key step towards more efficient energy conversion in the hydrogen industry of tomorrow.
As charge carriers, electrons and ions play the leading role in electrochemical energy storage devices and converters such as batteries and fuel cells. Proton...
Scientists from the Excellence Cluster Universe at the Ludwig-Maximilians-Universität Munich have establised "Cosmowebportal", a unique data centre for cosmological simulations located at the Leibniz Supercomputing Centre (LRZ) of the Bavarian Academy of Sciences. The complete results of a series of large hydrodynamical cosmological simulations are available, with data volumes typically exceeding several hundred terabytes. Scientists worldwide can interactively explore these complex simulations via a web interface and directly access the results.
With current telescopes, scientists can observe our Universe’s galaxies and galaxy clusters and their distribution along an invisible cosmic web. From the...
Temperature measurements possible even on the smallest scale / Molecular ruby for use in material sciences, biology, and medicine
Chemists at Johannes Gutenberg University Mainz (JGU) in cooperation with researchers of the German Federal Institute for Materials Research and Testing (BAM)...
19.06.2017 | Event News
13.06.2017 | Event News
13.06.2017 | Event News
23.06.2017 | Physics and Astronomy
23.06.2017 | Physics and Astronomy
23.06.2017 | Information Technology