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
One step closer to reality
20.04.2018 | Max-Planck-Institut für Entwicklungsbiologie
The dark side of cichlid fish: from cannibal to caregiver
20.04.2018 | Veterinärmedizinische Universität Wien
University of Connecticut researchers have created a biodegradable composite made of silk fibers that can be used to repair broken load-bearing bones without the complications sometimes presented by other materials.
Repairing major load-bearing bones such as those in the leg can be a long and uncomfortable process.
Study published in the journal ACS Applied Materials & Interfaces is the outcome of an international effort that included teams from Dresden and Berlin in Germany, and the US.
Scientists at the Helmholtz-Zentrum Dresden-Rossendorf (HZDR) together with colleagues from the Helmholtz-Zentrum Berlin (HZB) and the University of Virginia...
Novel highly efficient and brilliant gamma-ray source: Based on model calculations, physicists of the Max PIanck Institute for Nuclear Physics in Heidelberg propose a novel method for an efficient high-brilliance gamma-ray source. A giant collimated gamma-ray pulse is generated from the interaction of a dense ultra-relativistic electron beam with a thin solid conductor. Energetic gamma-rays are copiously produced as the electron beam splits into filaments while propagating across the conductor. The resulting gamma-ray energy and flux enable novel experiments in nuclear and fundamental physics.
The typical wavelength of light interacting with an object of the microcosm scales with the size of this object. For atoms, this ranges from visible light to...
Stable joint cartilage can be produced from adult stem cells originating from bone marrow. This is made possible by inducing specific molecular processes occurring during embryonic cartilage formation, as researchers from the University and University Hospital of Basel report in the scientific journal PNAS.
Certain mesenchymal stem/stromal cells from the bone marrow of adults are considered extremely promising for skeletal tissue regeneration. These adult stem...
In the fight against cancer, scientists are developing new drugs to hit tumor cells at so far unused weak points. Such a “sore spot” is the protein complex...
13.04.2018 | Event News
12.04.2018 | Event News
09.04.2018 | Event News
20.04.2018 | Physics and Astronomy
20.04.2018 | Physics and Astronomy
20.04.2018 | Physics and Astronomy