idw – Informationsdienst Wissenschaft
Nachrichten, Termine, Experten
Nachrichten, Termine, Experten
Study suggests zebrafish might teach us how to tackle Alzheimer’s disease
Patients with Alzheimer’s or other neurodegenerative diseases progressively loose neurons yet cannot build new ones. However, modulating the immune response might help the human brain to better cope with such conditions and regenerate. The research group led by Caghan Kizil at the German Center for Neurodegenerative Diseases (DZNE) in Dresden report on these findings in the journal “Cell Reports”. Their conclusions are based on studying zebrafish, an organism well-known for its ability to counteract neuronal damage by regenerating lost cells.
Zebrafish and humans are obviously quite different species. However, they share an evolutionary past that translates into various similarities on the cellular and molecular scale. “The regenerative skills apparent in zebrafish might lie dormant in humans and might somehow be activated by pulling the right strings”, Dr. Kizil explains. “This is why we study if and how zebrafish cope with neurodegeneration. We want to understand the basic molecular mechanisms of such a regenerative aptitude in order to design better clinical therapies.”
In the current study, the Dresden-based neuroscientist and his co-workers succeeded in mimicking symptoms of Alzheimer’s disease in zebrafish brain. Conditions were triggered by Amyloid-Beta42 (Aβ42) peptides – one of the major contributors to the disease in human brains. Similar to our brains, Amyloid molecules accumulated in the neurons of zebrafish leading to immune response, synaptic degeneration, cell death, learning deficits and other dysfunctions. “This is the first time, such conditions have been generated in adult zebrafish through Aβ42 deposits”, Kizil says.
The significance of neuro-immune crosstalk
The Aβ42 deposits triggered a special inflammation-related signaling pathway that ultimately lead to enhanced neurogenesis, i.e. new neurons were built. “We found that a molecule called Interleukin-4 is very much involved in the generation of neurons. The molecule is released by the dying neurons and immune system cells. It then acts on neural stem cells, which are the progenitors of neurons, by increasing their proliferation”, Kizil says. “Interleukin-4 has been known to be a player in immune response and inflammation. But to date, the direct role of IL4 on stem cell proliferation has not been shown.”
A better understanding of how we could manipulate inflammatory conditions might aid to develop novel therapies against Alzheimer’s, Kizil argues. “In humans inflammation does not seem to act as a positive cue for regeneration as it does in zebrafish. Possibly because other factors interfere in a complex manner. Our zebrafish model offers the opportunity to study such factors one by one in a reductionist manner. Besides, our study points to the significance of the immune response. That is to say: by tweaking the immune response, for example with drugs, and targeting the right cell types, we might unlock the potential of human neural stem cells to proliferate and build new neurons. Of course, the challenge remains as to what will happen to those new neurons. But first things first: we have to start from the stem cells.”
Original publication
“IL4/STAT6 signaling activates neural stem cell proliferation and neurogenesis upon Amyloid-β42 aggregation in adult zebrafish brain”, Prabesh Bhattarai, Alvin Kuriakose Thomas, Mehmet Ilyas Cosacak, Christos Papadimitriou, Violeta Mashkaryan, Cynthia Froc, Susanne Reinhardt, Thomas Kurth, Andreas Dahl, Yixin Zhang, Caghan Kizil, Cell Reports, DOI: 10.1016/j.celrep.2016.09.075
The German Center for Neurodegenerative Diseases (DZNE) investigates the causes of diseases of the nervous system and develops strategies for prevention, treatment and care. It is an institution within the Helmholtz Association of German Research Centres with nine sites across Germany (Berlin, Bonn, Dresden, Göttingen, Magdeburg, Munich, Rostock/Greifswald, Tübingen and Witten). The DZNE cooperates closely with universities, their clinics and other research facilities.
Web: www.dzne.de/en | Twitter: @dzne_en | Facebook: www.dzne.de/facebook
https://www.dzne.de/en/about-us/public-relations/news/2016/press-release-no-18.h...
Criteria of this press release:
Journalists, Scientists and scholars
Biology, Medicine
transregional, national
Research results
English
You can combine search terms with and, or and/or not, e.g. Philo not logy.
You can use brackets to separate combinations from each other, e.g. (Philo not logy) or (Psycho and logy).
Coherent groups of words will be located as complete phrases if you put them into quotation marks, e.g. “Federal Republic of Germany”.
You can also use the advanced search without entering search terms. It will then follow the criteria you have selected (e.g. country or subject area).
If you have not selected any criteria in a given category, the entire category will be searched (e.g. all subject areas or all countries).
