For many years researchers have observed protein deposits, also called aggregates, in the brains of patients with Alzheimer’s or Huntington’s disease. These aggregates are suspected to contribute to the death of nerve cells. As Science reports, researcher from the Max Planck Institute of Biochemistry in Martinsried, led by Mark Hipp and Ulrich Hartl, have now shown that the location of aggregates influences the survival of cells. While aggregates within the nucleus barely influence cellular function, deposits within the cytoplasm interfere with transport routes between the nucleus and the cytoplasm. In the long run this can lead to the death of the cells, and progression of the disease.
Proteins consist of long chains of amino acids and function in cells like small machines. To be able to fulfill their function proteins have to assume a predetermined three-dimensional structure. In healthy cells there is a large variety of folding helpers and extensive quality control machinery. Misfolded proteins are either repaired or rapidly degraded. If this occurs inadequately, or not at all, proteins will clump together, form aggregates and harm the cell.
Protein aggregates are associated with many neurodegenerative diseases including ALS, Alzheimer’s, Parkinson’s and Huntington’s Disease. How exactly aggregates harm cells is however still unknown. In 2013 several groups in Martinsried formed the ToPAG consortium (http://www.topag.mpg.de) to address this question, and can now report their first success. Scientists in the lab of Prof. Hartl, a world-renowned expert on protein folding, have demonstrated that the location of the aggregates determines the fate of the nerve cells.
Together with Konstanze Winklhofer and Jörg Tatzelt from the Ruhr-University Bochum, the researchers have expressed artificial aggregation prone proteins as well as Huntington’s disease-causing mutants of the protein huntingtin in cultured cells. Both types of protein accumulate in large protein deposits.
“It came as a big surprise to us that the direction of the proteins to the cytoplasm instead of the nucleus resulted in more soluble, but also more toxic aggregates”, says Mark Hipp, a group leader in the department of Ulrich Hartl and leader of the study. The protein deposits in the cytoplasm blocked the transport of RNA and correctly folded proteins between the nucleus and the cytoplasm. It seems that the sticky surfaces of the aggregates can sequester important proteins and thereby inactivate them.
“We have detected multiple components of the cellular transport machinery inside the aggregates. This results in the depletion of these factors from the cell, and, like a machine with missing parts, the cell is then unable to function properly”, explains Andreas Woerner the first author of the study.
Once the blueprint for all proteins, the RNA, is trapped within the nucleus, protein synthesis cannot progress, and the cells deteriorate. It is not completely clear why the nuclear aggregates are less harmful, but the researchers have evidence that the nuclear protein NPM1 plays a central role in shielding these aggregates.
“The results of this study bring us researchers and physicians one big step further”, summarizes Mark Hipp. “Only if we understand how aggregates damage cells is it possible to develop appropriate countermeasures in the future.”
C. Woerner, F. Frottin, D. Hornburg, L. R. Feng, F. Meissner, M. Patra, J. Tatzelt, M. Mann, K. F. Winklhofer, U. Hartl, M. S. Hipp: Cytoplasmic protein aggregates interfere with nucleo-cytoplasmic transport of protein and RNA. Science, January 2016
Dr. Mark S. Hipp
Department of Cellular Biochemistry
Max Planck Institute of Biochemistry
Am Klopferspitz 18
Dr. Christiane Menzfeld
Max Planck Institute of Biochemistry
Am Klopferspitz 18
Tel. +49 89 8578-2824
Dr. Christiane Menzfeld | Max-Planck-Institut für Biochemie
Don't Give the Slightest Chance to Toxic Elements in Medicinal Products
23.03.2018 | Physikalisch-Technische Bundesanstalt (PTB)
North and South Cooperation to Combat Tuberculosis
22.03.2018 | Universität Zürich
Satellites in near-Earth orbit are at risk due to the steady increase in space debris. But their mission in the areas of telecommunications, navigation or weather forecasts is essential for society. Fraunhofer FHR therefore develops radar-based systems which allow the detection, tracking and cataloging of even the smallest particles of debris. Satellite operators who have access to our data are in a better position to plan evasive maneuvers and prevent destructive collisions. From April, 25-29 2018, Fraunhofer FHR and its partners will exhibit the complementary radar systems TIRA and GESTRA as well as the latest radar techniques for space observation across three stands at the ILA Berlin.
The "traffic situation" in space is very tense: the Earth is currently being orbited not only by countless satellites but also by a large volume of space...
An international team of researchers has discovered a new anti-cancer protein. The protein, called LHPP, prevents the uncontrolled proliferation of cancer cells in the liver. The researchers led by Prof. Michael N. Hall from the Biozentrum, University of Basel, report in “Nature” that LHPP can also serve as a biomarker for the diagnosis and prognosis of liver cancer.
The incidence of liver cancer, also known as hepatocellular carcinoma, is steadily increasing. In the last twenty years, the number of cases has almost doubled...
In just a few weeks from now, the Chinese space station Tiangong-1 will re-enter the Earth's atmosphere where it will to a large extent burn up. It is possible that some debris will reach the Earth's surface. Tiangong-1 is orbiting the Earth uncontrolled at a speed of approx. 29,000 km/h.Currently the prognosis relating to the time of impact currently lies within a window of several days. The scientists at Fraunhofer FHR have already been monitoring Tiangong-1 for a number of weeks with their TIRA system, one of the most powerful space observation radars in the world, with a view to supporting the German Space Situational Awareness Center and the ESA with their re-entry forecasts.
Following the loss of radio contact with Tiangong-1 in 2016 and due to the low orbital height, it is now inevitable that the Chinese space station will...
Fraunhofer Institute for Organic Electronics, Electron Beam and Plasma Technology FEP, provider of research and development services for OLED lighting solutions, announces the founding of the “OLED Licht Forum” and presents latest OLED design and lighting solutions during light+building, from March 18th – 23rd, 2018 in Frankfurt a.M./Germany, at booth no. F91 in Hall 4.0.
They are united in their passion for OLED (organic light emitting diodes) lighting with all of its unique facets and application possibilities. Thus experts in...
A new scenario seeking to explain how Mars' putative oceans came and went over the last 4 billion years implies that the oceans formed several hundred million...
23.03.2018 | Event News
19.03.2018 | Event News
16.03.2018 | Event News
23.03.2018 | Materials Sciences
23.03.2018 | Agricultural and Forestry Science
23.03.2018 | Physics and Astronomy