Researchers at the German Center for Neurodegenerative Diseases (DZNE) and the University Medical Center Göttingen (UMG) have identified an enzyme as a possible target for the treatment of Alzheimer’s disease. The protein known as HDAC6 impairs transport processes within the nerve cells. The scientists observed only mild symptoms of the disease in mice if the enzyme was not produced. They propose to block its activity in a targeted fashion to treat the disease.
The HDAC6 protein (green) regulates the transportation of mitochondria – the cell’s power plants – along ‘microtubule highways’ (red) inside nerve cells (nucleus shown in blue). This process is inhibited in Alzheimer’s nerve cells and can be returned to normal by switching off HDAC6.
Source: André Fischer
Scientists from the DZNE sites in Göttingen and Bonn, the UMG as well as from the US participated in this basic research project on Alzheimer’s disease. The study is published in "EMBO Molecular Medicine".
The researchers led by Prof. André Fischer, Department of Psychiatry and Psychotherapy at the University Medical Center Gottingen and Site Speaker of the DZNE in Göttingen, investigated mice with a modified genetic background. The animals showed behavioural disorders and brain deposits that are typically associated with Alzheimer’s disease. The researchers went a step further with a group of other animals by removing the genes responsible for the production of the HDAC6 enzyme (histone deacetylase 6). This intervention proved to be effective: while these mice also exhibited the pathological features of Alzheimer’s disease in the brain, their behaviour was significantly ameliorated. "The animals’ ability to learn and to find their spatial bearings was relatively normal", says Prof. Fischer. "Their cognitive abilities were fully comparable to those of healthy mice."
Improved cellular traffic
In the researchers’ view, this effect is at least partly attributable to the fact that important transport processes within the nerve cells are facilitated when the HDAC6 enzyme is not around. This meant in particular that the cells’ power plants, also known as "mitochondria", can travel to their final destinations. "It is known that in various neurodegenerative diseases cellular transport is no longer functional. The substances that are to be transported along axons are left behind", Fischer says. "Measures which improve trafficking seem to have a positive effect."
Possible target for therapy?
The researchers’ findings suggest that the HDAC6 enzyme could be a possible target for therapies against Alzheimer’s disease. However, treatments would require an active substance that can disable the enzyme in a targeted fashion. Unfortunately, the active substances known to date are too unspecific. Prof. Fischer explains that their application resembles a broad-spectrum treatment: "We don’t know precisely what is the therapeutic effect of the inhibitors, since they simultaneously block several enzymes from the histone deacetylase family", he says. "And we still don’t know enough about how the individual enzymes function".
Improving the accuracy of the inhibitors is therefore the aim of further research. "We will continue to work toward this goal. On one hand, we want to improve our understanding of how the various histone deacetylases function. On the other hand, we want to test inhibitors that operate in a more targeted manner", says Prof. André Fischer.Original publication:
The German Center for Neurodegenerative Diseases (DZNE) investigates the causes of diseases of the nervous system and develops strategies for prevention, treatment and care. It is an institution of the Helmholtz Association of German Research Centres with sites in Berlin, Bonn, Dresden, Göttingen, Magdeburg, Munich, Rostock/Greifswald, Tübingen and Witten. The DZNE cooperates closely with universities, their clinics and other research facilities. Its cooperation partners in Göttingen are the Georg-August-University and the University Medical Center Göttingen. Website: http://www.dzne.de/en
Dr. Marcus Neitzert | idw
Supercoiled DNA is far more dynamic than the 'Watson-Crick' double helix
13.10.2015 | University of Leeds
New Oregon approach for 'nanohoops' could energize future devices
13.10.2015 | University of Oregon
Physicists of TU Berlin and mathematicians of MATHEON are so successful that even the prestigious journal “Nature Communications” reported on their project.
Security in data transfer is an important issue, and not only since the NSA scandal. Sometimes, however, the need for speed conflicts to a certain degree with...
Having a light touch can make a hefty difference in how well animals and robots move across challenging granular surfaces such as snow, sand and leaf litter. Research reported October 9 in the journal Bioinspiration & Biomimetics shows how the design of appendages – whether legs or wheels – affects the ability of both robots and animals to cross weak and flowing surfaces.
Using an air fluidized bed trackway filled with poppy seeds or glass spheres, researchers at the Georgia Institute of Technology systematically varied the...
Nondestructive material testing (NDT) is a fast and effective way to analyze the quality of a product during the manufacturing process. Because defective materials can lead to malfunctioning finished products, NDT is an essential quality assurance measure, especially in the manufacture of safety-critical components such as automotive B-pillars. NDT examines the quality without damaging the component or modifying the surface of the material. At this year's Blechexpo trade fair in Stuttgart, Fraunhofer IZFP will have an exhibit that demonstrates the nondestructive testing of high-strength automotive body parts using 3MA. The measurement results are available in a matter of seconds.
To minimize vehicle weight and fuel consumption while providing the highest level of crash safety, automotive bodies are reinforced with elements made from...
The MICADO camera, a first light instrument for the European Extremely Large Telescope (E-ELT), has entered a new phase in the project: by agreeing to a Memorandum of Understanding, the partners in Germany, France, the Netherlands, Austria, and Italy, have all confirmed their participation. Following this milestone, the project's transition into its preliminary design phase was approved at a kick-off meeting held in Vienna. Two weeks earlier, on September 18, the consortium and the European Southern Observatory (ESO), which is building the telescope, have signed the corresponding collaboration agreement.
As the first dedicated camera for the E-ELT, MICADO will equip the giant telescope with a capability for diffraction-limited imaging at near-infrared...
Self-driving cars will be on our streets in the foreseeable future. In Graz, research is currently dedicated to an innovative driver assistance system that takes over control if there is a danger of collision. It was nature that inspired Dr Manfred Hartbauer from the Institute of Zoology at the University of Graz: in dangerous traffic situations, migratory locusts react around ten times faster than humans. Working together with an interdisciplinary team, Hartbauer is investigating an affordable collision detector that is equipped with artificial locust eyes and can recognise potential crashes in time, during both day and night.
Inspired by insects
01.10.2015 | Event News
30.09.2015 | Event News
17.09.2015 | Event News
13.10.2015 | Trade Fair News
13.10.2015 | Physics and Astronomy
13.10.2015 | Health and Medicine