A team of European scientists from the University Medical Center Hamburg-Eppendorf (UKE) and the Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD) at the University of Cologne in Germany has taken an important step closer to understanding the root cause of age-related dementia.
In research involving both worms and mice, they have found that age-related dementia is likely the result of a declining ability of neurons to dispose of unwanted aggregated proteins. As protein disposal becomes significantly less efficient with increasing age, the buildup of these unwanted proteins ultimately leads to the development and progression of dementia. This research appears in the March 2013 issue of the journal Genetics (http://www.genetics.org).
"By studying disease progression in dementia, specifically by focusing on mechanisms neurons use to dispose of unwanted proteins, we show how these are interconnected and how these mechanisms deteriorate over time," said Markus Glatzel, M.D., a researcher involved in the work from the Institute of Neuropathology at UKE in Hamburg, Germany. "This gives us a better understanding as to why dementias affect older persons; the ultimate aim is to use these insights to devise novel therapies to restore the full capacity of protein disposal in aged neurons."
To make this discovery, scientists carried out their experiments in both worm and mouse models that had a genetically-determined dementia in which the disease was caused by protein accumulation in neurons. In the worm model, researchers in the lab of Thorsten Hoppe, Ph.D., from the CECAD Cluster of Excellence could inactivate distinct routes used for the disposal of the unwanted proteins. Results provided valuable insight into the mechanisms that neurons use to cope with protein accumulation. These pathways were then assessed in young and aged mice. This study provides an explanation of why dementias exponentially increase with age. Additionally, neuron protein disposal methods may offer a therapeutic target for the development of drugs to treat and/or prevent dementias.
"This is an exciting study that helps us understand what's going wrong at a cellular level in age-related dementias," said Mark Johnston, Ph.D., Editor-in-Chief of the journal Genetics. "This research holds possibilities for future identification of substances that can prevent, stop, or reverse this cellular malfunction in humans."
CITATION: Schipanski, Angela, Sascha Lange, Alexandra Segref, Aljona Gutschmidt, David A. Lomas, Elena Miranda, Michaela Schweizer, Thorsten Hoppe, and Markus Glatzel A Novel Interaction between Aging and ER Overload in a Protein Conformational Dementia Genetics March 2013, 193: 865-876.
FUNDING: This work is supported by grants of the Deutsche Forschungsgemeinschaft (especially the FOR885 to M.G. and T.H., the Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD) to T.H. and GRK1459 to M.G.), the Medical Research Council (UK) to D.L., the Hans und Ilse Breuer Foundation to S.L., the Leibniz Center Infection Graduate School (Model systems for infectious diseases), and the Landesexzellenzinitiative of Hamburg (SDI-LEXI) to M.G.
ABOUT GENETICS: Since 1916, Genetics (http://www.genetics.org/) has covered high quality, original research on a range of topics bearing on inheritance, including population and evolutionary genetics, complex traits, developmental and behavioral genetics, cellular genetics, gene expression, genome integrity and transmission, and genome and systems biology. Genetics, a peer-reviewed, peer-edited journal of the Genetics Society of America is one of the world's most cited journals in genetics and heredity.
ABOUT GSA: Founded in 1931, the Genetics Society of America (GSA) is the professional membership organization for scientific researchers, educators, bioengineers, bioinformaticians and others interested in the field of genetics. Its nearly 5,000 members work to advance knowledge in the basic mechanisms of inheritance, from the molecular to the population level. The GSA is dedicated to promoting research in genetics and to facilitating communication among geneticists worldwide through its conferences, including the biennial conference on Model Organisms to Human Biology, an interdisciplinary meeting on current and cutting edge topics in genetics research, as well as annual and biennial meetings that focus on the genetics of particular organisms, including C. elegans, Drosophila, fungi, mice, yeast, and zebrafish. GSA publishes Genetics, a leading journal in the field and an online, open-access journal, G3: Genes|Genomes|Genetics. For more information about GSA, please visit http://www.genetics-gsa.org. Also follow GSA on Facebook at facebook.com/GeneticsGSA and on Twitter @GeneticsGSA.
Phyllis Edelman | EurekAlert!
Two decades of training students and experts in tracking infectious disease
27.11.2015 | Hochschule für Angewandte Wissenschaften Hamburg
Increased carbon dioxide enhances plankton growth, opposite of what was expected
27.11.2015 | Bigelow Laboratory for Ocean Sciences
Planet Earth experienced a global climate shift in the late 1980s on an unprecedented scale, fuelled by anthropogenic warming and a volcanic eruption, according to new research published this week.
Scientists say that a major step change, or ‘regime shift’, in the Earth’s biophysical systems, from the upper atmosphere to the depths of the ocean and from...
The Fraunhofer Institute for Solar Energy Systems ISE has installed 70 photovoltaic modules on the outer façade of one of its lab buildings. The modules were...
Nerve cells cover their high energy demand with glucose and lactate. Scientists of the University of Zurich now provide new support for this. They show for the first time in the intact mouse brain evidence for an exchange of lactate between different brain cells. With this study they were able to confirm a 20-year old hypothesis.
In comparison to other organs, the human brain has the highest energy requirements. The supply of energy for nerve cells and the particular role of lactic acid...
In laser material processing, the simulation of processes has made great strides over the past few years. Today, the software can predict relatively well what will happen on the workpiece. Unfortunately, it is also highly complex and requires a lot of computing time. Thanks to clever simplification, experts from Fraunhofer ILT are now able to offer the first-ever simulation software that calculates processes in real time and also runs on tablet computers and smartphones. The fast software enables users to do without expensive experiments and to find optimum process parameters even more effectively.
Before now, the reliable simulation of laser processes was a job for experts. Armed with sophisticated software packages and after many hours on computer...
Researchers at Heidelberg University have devised a new way to study the phenomenon of magnetism. Using ultracold atoms at near absolute zero, they prepared a...
25.11.2015 | Event News
17.11.2015 | Event News
21.10.2015 | Event News
27.11.2015 | Press release
27.11.2015 | Life Sciences
27.11.2015 | Materials Sciences