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!
How to become a T follicular helper cell
31.07.2015 | La Jolla Institute for Allergy and Immunology
Heating and cooling with light leads to ultrafast DNA diagnostics
31.07.2015 | University of California - Berkeley
Using ultracold atoms trapped in light crystals, scientists from the MPQ, LMU, and the Weizmann Institute observe a novel state of matter that never thermalizes.
What happens if one mixes cold and hot water? After some initial dynamics, one is left with lukewarm water—the system has thermalized to a new thermal...
Physicists from Regensburg and Marburg, Germany have succeeded in taking a slow-motion movie of speeding electrons in a solid driven by a strong light wave. In the process, they have unraveled a novel quantum phenomenon, which will be reported in the forthcoming edition of Nature.
The advent of ever faster electronics featuring clock rates up to the multiple-gigahertz range has revolutionized our day-to-day life. Researchers and...
Researchers have developed an ultrafast light-emitting device that can flip on and off 90 billion times a second and could form the basis of optical computing.
Joint BioEnergy Institute study identifies bacterial protein that is key to protecting rice against bacterial blight
A bacterial signal that when recognized by rice plants enables the plants to resist a devastating blight disease has been identified by a multi-national team...
Researchers in the Cockrell School of Engineering at The University of Texas at Austin are one step closer to delivering smart windows with a new level of energy efficiency, engineering materials that allow windows to reveal light without transferring heat and, conversely, to block light while allowing heat transmission, as described in two new research papers.
By allowing indoor occupants to more precisely control the energy and sunlight passing through a window, the new materials could significantly reduce costs for...
23.07.2015 | Event News
10.07.2015 | Event News
25.06.2015 | Event News
31.07.2015 | Trade Fair News
31.07.2015 | Transportation and Logistics
31.07.2015 | Physics and Astronomy