The research team of Dr. Caghan Kizil at the DFG-Center for Regenerative Therapies Dresden (CRTD) - Cluster of Excellence at the TU Dresden, achieved a major advance in Alzheimer’s research. They showed how a diseased vertebrate brain can naturally react to Alzheimer’s pathology by forming more neurons. Two proteins (Interleukin-4 and STAT6) have been identified to be relevant for this process. This is a big step towards the understanding, prevention or even healing of Alzheimer’s disease – a disease with about 170,000 new cases diagnosed every year in Germany. The results have been published in the scientific journal Cell Reports this week.
Alzheimer's disease is the most common form of dementia. Affected people are troubled with symptoms like memory loss, disorientation or changes in behavior. Patients are affected in their day-to-day life and are dependent on the help of others. Alzheimer's disease accounts for 60 to 80 percent of dementia cases worldwide, mainly affecting people above the age of 65. Alzheimer's disease has no current cure, which together with the high number of new cases each year emphasizes the high relevance of research in this field.
The image shows the spatial organization of immune cells (green) and neurons (red) on a cross section of adult zebrafish forebrain (cell nuclei: blue).
© Kizil Lab
The study of the laboratory of Dr. Caghan Kizil used the animal model zebrafish, which can regenerate their brain. Zebrafish have an extensive ability to replenish the lost neurons after various types of damage, and the team led by Dr. Kizil showed that it can also do so after Alzheimer-like neurodegeneration. This is an ability humans do not have. Evolutionarily, the zebrafish and human beings are very similar: the cell types in the zebrafish brain and their physiological roles are very similar to humans, and more than 80 percent of the genes humans have are identical in the zebrafish.
Therefore, zebrafish are an ideal model for studying complex diseases of humans in a very simplistic way. “We believe that understanding how zebrafish can cope with neurodegeneration would help us to design clinical therapy options for humans, such as for Alzheimer's disease. Within this study, we observed Alzheimer-like conditions in the fish brain. We found that zebrafish can impressively increase the neural stem cell proliferation and formation of new neurons even after Alzheimer's-like pathology. This is amazing because to treat Alzheimer's we need to generate more neurons. And this all starts with neural stem cell proliferation, which fails in our diseased brains”, Caghan Kizil explains.
This study has shown that Alzheimer's disease symptoms can be recapitulated in the zebrafish brain using a short section of human APP protein that is a hallmark of Alzheimer's disease (Amyloid-β42). This protein part causes the death of neurons, inflammation, loss of neuronal connections and deficits in memory formation in zebrafish. Caghan Kizil’s research group including the lead author involved in the study, Prabesh Bhattarai, found that the immune-related molecule Interleukin-4 (which is also present in the human brain) is produced by the immune cells and dying neurons in the fish brain.
This molecule alerts the neural stem cells that there is danger around. Stem cells then start to proliferatethrough a cell-intrinsic mechanism involving another protein of central function called STAT6. The importance of this study lies in the notion that the diseased brain and the inflammatory milieu there can be modulated to kick-start neural stem cell proliferation, and this is exactly what successfully regenerating vertebrates do.
The next steps towards an understanding of Alzheimer’s disease are clearly defined: “We will go on identifying more factors required for a successful ‘regeneration’ response in fish brain after an Alzheimer's disease-like situation. By doing so, we can get a more complete picture of the molecular programs beneficial for tackling this atrocious disease. Zebrafish will tell us the candidate genes we should focus on in our brains for possible regenerative therapies. I believe that we can come up with meaningful therapies only by combining an increase inthe proliferation of stem cells with the existing methods of prevention (existing drugs, rehabilitation approaches, preventive precautions etc.)”, Caghan Kizil says.
Since 2014, Caghan Kizil works as research group leader at the CRTD, where he also completed his Postdoc position from 2009-2014. Before completing his PhD at the Max Planck Institute for Developmental Biology (Tübingen, Germany), Caghan Kizil gained his Master’s degree from Max Planck Institute for Biophysical Chemistry (Göttingen, Germany) and his Bachelor degree from Middle East Technical University (Ankara, Turkey). He is a Helmholtz Young Investigator Group Leader in German Center for Neurodegenerative Diseases (DZNE).
“IL4/STAT6 signaling activates neural stem cell proliferation and neurogenesis upon
Amyloid-β42 in adult zebrafish brain”
Kizil Lab Facebook Page
Franziska Clauß, M.A.
Phone: +49 351 458 82065
Founded in 2006, the DFG Research Center for Regenerative Therapies Dresden (CRTD), Cluster of Excellence at the TU Dresden has now passed the second phase of the Excellence Initiative which aims to promote top-level research and improve the quality of German universities and research institutions. The goal of the CRTD is to explore the human body's regenerative potential and to develop completely new, regenerative therapies for hitherto incurable diseases. The key areas of research include haematology and immunology, diabetes, neurodegenerative diseases, and bone regeneration. At present, eight professors and ten group leaders are working at the CRTD – integrated into an interdisciplinary network of 87 members at seven different institutions within Dresden. In addition, 21 partners from industry are supporting the network. The synergies in the network allow for a fast translation of results from basic research to clinical applications.
Franziska Clauß | idw - Informationsdienst Wissenschaft
Researchers identify how bacterium survives in oxygen-poor environments
22.11.2017 | Columbia University
Researchers discover specific tumor environment that triggers cells to metastasize
22.11.2017 | University of California - San Diego
The WHO reports an estimated 429,000 malaria deaths each year. The disease mostly affects tropical and subtropical regions and in particular the African continent. The Fraunhofer Institute for Silicate Research ISC teamed up with the Fraunhofer Institute for Molecular Biology and Applied Ecology IME and the Institute of Tropical Medicine at the University of Tübingen for a new test method to detect malaria parasites in blood. The idea of the research project “NanoFRET” is to develop a highly sensitive and reliable rapid diagnostic test so that patient treatment can begin as early as possible.
Malaria is caused by parasites transmitted by mosquito bite. The most dangerous form of malaria is malaria tropica. Left untreated, it is fatal in most cases....
The formation of stars in distant galaxies is still largely unexplored. For the first time, astron-omers at the University of Geneva have now been able to closely observe a star system six billion light-years away. In doing so, they are confirming earlier simulations made by the University of Zurich. One special effect is made possible by the multiple reflections of images that run through the cosmos like a snake.
Today, astronomers have a pretty accurate idea of how stars were formed in the recent cosmic past. But do these laws also apply to older galaxies? For around a...
Just because someone is smart and well-motivated doesn't mean he or she can learn the visual skills needed to excel at tasks like matching fingerprints, interpreting medical X-rays, keeping track of aircraft on radar displays or forensic face matching.
That is the implication of a new study which shows for the first time that there is a broad range of differences in people's visual ability and that these...
Computer Tomography (CT) is a standard procedure in hospitals, but so far, the technology has not been suitable for imaging extremely small objects. In PNAS, a team from the Technical University of Munich (TUM) describes a Nano-CT device that creates three-dimensional x-ray images at resolutions up to 100 nanometers. The first test application: Together with colleagues from the University of Kassel and Helmholtz-Zentrum Geesthacht the researchers analyzed the locomotory system of a velvet worm.
During a CT analysis, the object under investigation is x-rayed and a detector measures the respective amount of radiation absorbed from various angles....
The quantum world is fragile; error correction codes are needed to protect the information stored in a quantum object from the deteriorating effects of noise. Quantum physicists in Innsbruck have developed a protocol to pass quantum information between differently encoded building blocks of a future quantum computer, such as processors and memories. Scientists may use this protocol in the future to build a data bus for quantum computers. The researchers have published their work in the journal Nature Communications.
Future quantum computers will be able to solve problems where conventional computers fail today. We are still far away from any large-scale implementation,...
15.11.2017 | Event News
15.11.2017 | Event News
30.10.2017 | Event News
22.11.2017 | Medical Engineering
22.11.2017 | Materials Sciences
22.11.2017 | Health and Medicine