By studying the skin phenotype of the hereditary disease Cockayne syndrome researchers at the IUF and HHU Düsseldorf have found a mechanism which can prevent the loss of subcutaneous fat, i.e. one of the cardinal symptoms of Cockayne syndrome. This study was now published in “Science Translational Medicine”.
The Cockayne syndrome is a very rare hereditary disease, which can lead among others to dwarfism, neurological impairment, premature aging and a shortened life span. Skin symptoms include a striking sensitivity to UV rays and a dramatic loss of subcutaneous fat.
The disease is caused in 80 % of the cases by a mutation in the CSB gene. There is no curative treatment. The CSB protein is well known for its role in DNA repair and the Cockayne syndrome therefore usually described as a DNA repair deficiency syndrome. This view, however, does not explain the diverse clinical phenotype of the patients and hence, the CSB protein most likely serves important biological functions beyond DNA repair.
A study of the IUF – Leibniz Research Institute for Environmental Medicine and the Heinrich Heine University Düsseldorf (HHU), Germany, now shows for the first time that the CSB protein is not only present in the nucleus but also at the centrosome of the cell where it enhances acetylation (a certain modification) of α-Tubulin (a protein which forms routes of transportation in the cell) and thereby regulates autophagy (the degradation of cellular material in the cell fluid).
If the protein is not able to fulfill this task, an imbalance in protein acetylation occurs. Administration of the histone deacetylase inhibitor SAHA, which inhibits a certain protein family in reversing acetylation, was able to restore this balance. Of note, the loss of subcutaneous fat, i.e. a hallmark of Cockayne syndrome B, could also be restored by SAHA in the mouse model.
These results, which have been generated across several species including nematodes, mice and human skin cells, were now published in “Science Translational Medicine”. Future studies will assess if the HDAC inhibitor SAHA, which is a FDA approved drug for treating certain forms of cutaneous T cell lymphoma, is also suitable for the treatment of patients with Cockayne syndrome.
“More and more biological functions beyond DNA repair are being discovered for proteins, which were originally described as DNA repair enzymes. Examples are the CSB protein but also the XPA protein which causes a very severe subtype of Xeroderma pigmentosum”, says Prof. Jean Krutmann, director of the IUF. “This paradigm shift might allow us to identify new strategies for the treatment of these incurable diseases”.
The investigations with the nematodes were conducted by a liaison group between the IUF and the Central Institute of Clinical Chemistry and Laboratory Medicine of the Heinrich Heine University in Düsseldorf, Germany, which is led by Dr. Natascia Ventura.
About the IUF
The IUF – Leibniz Research Institute for Environmental Medicine investigates the molecular mechanisms through which particles, radiation and environmental chemicals harm human health. The main working areas are environmentally induced aging of the cardiopulmonary system and the skin as well as disturbances of the nervous and immune system. Through development of novel model systems the IUF contributes to the improvement of risk assessment and the identification of novel strategies for the prevention / therapy of environmentally induced health damage.
More information: http://www.iuf-duesseldorf.com.
The IUF is part of the Leibniz Association: http://www.leibniz-gemeinschaft.de/en/home.
Christiane Klasen, Personal Assistant to the institute’s Director
IUF – Leibniz Research Institute for Environmental Medicine
Auf’m Hennekamp 50
Phone: +49 (0)211 3389 216
Majora M, Sondenheimer K, Knechten M, Uthe I, Esser C, Schiavi A, Ventura N, Krutmann J: HDAC inhibition improves autophagic and lysosomal function to prevent loss of subcutaneous fat in a mouse model of Cockayne syndrome. Sci Transl Med 10: eaam7510, 2018. doi: 10.1126/scitranslmed.aam7510
Christiane Klasen | idw - Informationsdienst Wissenschaft
Elusive compounds of greenhouse gas isolated by Warwick chemists
18.09.2019 | University of Warwick
Study gives clues to the origin of Huntington's disease, and a new way to find drugs
18.09.2019 | Rockefeller University
Researchers from the Department of Atomically Resolved Dynamics of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg, the University of Hamburg and the European Molecular Biology Laboratory (EMBL) outstation in the city have developed a new method to watch biomolecules at work. This method dramatically simplifies starting enzymatic reactions by mixing a cocktail of small amounts of liquids with protein crystals. Determination of the protein structures at different times after mixing can be assembled into a time-lapse sequence that shows the molecular foundations of biology.
The functions of biomolecules are determined by their motions and structural changes. Yet it is a formidable challenge to understand these dynamic motions.
At the International Symposium on Automotive Lighting 2019 (ISAL) in Darmstadt from September 23 to 25, 2019, the Fraunhofer Institute for Organic Electronics, Electron Beam and Plasma Technology FEP, a provider of research and development services in the field of organic electronics, will present OLED light strips of any length with additional functionalities for the first time at booth no. 37.
Almost everyone is familiar with light strips for interior design. LED strips are available by the metre in DIY stores around the corner and are just as often...
Later during this century, around 2060, a paradigm shift in global energy consumption is expected: we will spend more energy for cooling than for heating....
Researchers from the Department of Atomically Resolved Dynamics of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg, the University of Potsdam (both in Germany) and the University of Toronto (Canada) have pieced together a detailed time-lapse movie revealing all the major steps during the catalytic cycle of an enzyme. Surprisingly, the communication between the protein units is accomplished via a water-network akin to a string telephone. This communication is aligned with a ‘breathing’ motion, that is the expansion and contraction of the protein.
This time-lapse sequence of structures reveals dynamic motions as a fundamental element in the molecular foundations of biology.
Two research teams have succeeded simultaneously in measuring the long-sought Thorium nuclear transition, which enables extremely precise nuclear clocks. TU Wien (Vienna) is part of both teams.
If you want to build the most accurate clock in the world, you need something that "ticks" very fast and extremely precise. In an atomic clock, electrons are...
10.09.2019 | Event News
04.09.2019 | Event News
29.08.2019 | Event News
18.09.2019 | Innovative Products
18.09.2019 | Physics and Astronomy
18.09.2019 | Materials Sciences