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
Barium ruthenate: A high-yield, easy-to-handle perovskite catalyst for the oxidation of sulfides
16.07.2018 | Tokyo Institute of Technology
The secret sulfate code that lets the bad Tau in
16.07.2018 | American Society for Biochemistry and Molecular Biology
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
16.07.2018 | Physics and Astronomy
16.07.2018 | Life Sciences
16.07.2018 | Earth Sciences