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
Scientists uncover the role of a protein in production & survival of myelin-forming cells
19.07.2018 | Advanced Science Research Center, GC/CUNY
NYSCF researchers develop novel bioengineering technique for personalized bone grafts
18.07.2018 | New York Stem Cell Foundation
For the first time ever, scientists have determined the cosmic origin of highest-energy neutrinos. A research group led by IceCube scientist Elisa Resconi, spokesperson of the Collaborative Research Center SFB1258 at the Technical University of Munich (TUM), provides an important piece of evidence that the particles detected by the IceCube neutrino telescope at the South Pole originate from a galaxy four billion light-years away from Earth.
To rule out other origins with certainty, the team led by neutrino physicist Elisa Resconi from the Technical University of Munich and multi-wavelength...
For the first time a team of researchers have discovered two different phases of magnetic skyrmions in a single material. Physicists of the Technical Universities of Munich and Dresden and the University of Cologne can now better study and understand the properties of these magnetic structures, which are important for both basic research and applications.
Whirlpools are an everyday experience in a bath tub: When the water is drained a circular vortex is formed. Typically, such whirls are rather stable. Similar...
Physicists working with Roland Wester at the University of Innsbruck have investigated if and how chemical reactions can be influenced by targeted vibrational excitation of the reactants. They were able to demonstrate that excitation with a laser beam does not affect the efficiency of a chemical exchange reaction and that the excited molecular group acts only as a spectator in the reaction.
A frequently used reaction in organic chemistry is nucleophilic substitution. It plays, for example, an important role in in the synthesis of new chemical...
Optical spectroscopy allows investigating the energy structure and dynamic properties of complex quantum systems. Researchers from the University of Würzburg present two new approaches of coherent two-dimensional spectroscopy.
"Put an excitation into the system and observe how it evolves." According to physicist Professor Tobias Brixner, this is the credo of optical spectroscopy....
Ultra-short, high-intensity X-ray flashes open the door to the foundations of chemical reactions. Free-electron lasers generate these kinds of pulses, but there is a catch: the pulses vary in duration and energy. An international research team has now presented a solution: Using a ring of 16 detectors and a circularly polarized laser beam, they can determine both factors with attosecond accuracy.
Free-electron lasers (FELs) generate extremely short and intense X-ray flashes. Researchers can use these flashes to resolve structures with diameters on the...
13.07.2018 | Event News
12.07.2018 | Event News
03.07.2018 | Event News
19.07.2018 | Life Sciences
19.07.2018 | Earth Sciences
19.07.2018 | Social Sciences