Kizil Lab

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Mechanisms of the induced plasticity of the vertebrate brain


Our main goals in DZNE are

- To learn from zebrafish how to enable the adult brains to better cope with neurodegenerative disease and regenerate

- To identify the molecular mechanisms of neural stem cell plasticity in adult zebrafish brain after neurodegeneration

- To generate humanized models of Alzheimer's disease and perform comp

arative studies

The brains of aging humans are prone to neurodegenerative disorders and we humans are unable to counteract neuronal loss by regenerating lost cells. Patients with neurodegenerative conditions progressively loose neurons yet cannot form new neurons that would replace the lost ones. However, in nature, several vertebrates such as zebrafish bear a widespread regenerative ability that includes replenishment of neurons in the adult central nervous system due to the neurogenic activity of the progenitor cells. We have recently identified that this regenerative ability in fish requires turning on special molecular programs of the neural progenitor cells that in the end make regenerative neurogenesis possible. These findings suggest that regenerating organisms such as zebrafish could use special molecular programs to modulate the plasticity of the neural stem cells and enable restoration of compromised neural tissues. Hypothetically, these programs might also underlie the disparity between the regenerative capacities of zebrafish brain and mammalian brains. Therefore, neurodegenerative diseases of humans can be considered to some degree also as “stem cell diseases”. The main motivation for our research group at DZNE in Dresden is to understand what it takes in terms of molecular programs for zebrafish brain to regenerate itself after neurodegeneration, and which parts of those relevant molecular programs are missing in mammalian brains.

We have discovered a genetic variant in the   gene that significantly lowers the risk of  's disease. Found in individua...
04/14/2024

We have discovered a genetic variant in the gene that significantly lowers the risk of 's disease. Found in individuals resistant to Alzheimer's despite high risk, our findings point towards novel strategies for developing drugs to combat Alzheimer’s.

For more details, visit our full article:

The risk of developing Alzheimer’s disease (AD) significantly increases in individuals carrying the APOEε4 allele. Elderly cognitively healthy individuals with APOEε4 also exist, suggesting the presence of cellular mechanisms that counteract the pathological effects of APOEε4; however, these me...

Our lab moved to New York to the Department of Neurology and the Taub Institute in Columbia University Irving Medical Ce...
01/03/2023

Our lab moved to New York to the Department of Neurology and the Taub Institute in Columbia University Irving Medical Center. We are thrilled to continue and expand on our work in zebrafish on Alzheimer’s disease in the great New York City at this great university!

We are glad to have this important publication out! This was a beautiful collaborative work in Columbia University Irvin...
05/26/2022

We are glad to have this important publication out! This was a beautiful collaborative work in Columbia University Irving Medical Center.

Clinical studies and basic science met to identify the gene FMNL2, which regulates the function of a critical structure in our brains: blood-brain-barrier. FMNL2 links cerebrovascular disease and Alzheimer’s! We are one step closer now to understand how cardiovascular diseases increase the risk of Alzheimer's disease. We provide evidence from zebrafish, mouse and human brains

For more info:
https://www.cuimc.columbia.edu/news/missing-link-between-alzheimers-and-vascular-disease-found

Original publication in Acta Neuropathologica:
https://doi.org/10.1007/s00401-022-02431-6

Alzheimer’s disease (AD) has been associated with cardiovascular and cerebrovascular risk factors (CVRFs) during middle age and later and is frequently accompanied by cerebrovascular pathology at death. An interaction between CVRFs and genetic variants might explain the pathogenesis. Genome-wide, ...

A nice article in The Scientist on the role and future promises of adult   in  's disease. The article also features our...
02/03/2021

A nice article in The Scientist on the role and future promises of adult in 's disease. The article also features our previous work in PLOS Biology.

Manipulating the production of new neurons can improve cognition in animal models of the disease, raising the possibility that figuring out a way for humans to make more neurons could make a difference for people with dementia.

Prbs Bhattarai successfully defended his   thesis and graduated from our lab! Prabesh published 15 papers in respected j...
10/23/2020

Prbs Bhattarai successfully defended his thesis and graduated from our lab! Prabesh published 15 papers in respected journals during his PhD with a remarkable record. We wish him all the best for his successful career. Prabesh generated an Alzheimer’s disease model in , and identified molecular mechanisms controlling neural stem cell plasticity in experimental AD conditions in the adult fish for the first time. His contributions are significant. We are grateful for his efforts! Great job Prabesh!

We are glad to announce a review we wrote together with Nathalie Jurisch-Yaksi and Emre Yaksi is now published as an ope...
06/01/2020

We are glad to announce a review we wrote together with Nathalie Jurisch-Yaksi and Emre Yaksi is now published as an open access article in the journal GLIA.

We compare glial cells and their functions in zebrafish and mammals. Glia research is a growing field and we hope that our publication will contribute to this research area.

Thanks to the funding agencies and institutes that supported this work: Kavli Institute for Systems Neuroscience, NTNU - Norges teknisk-naturvitenskapelige universitet, TU Dresden, Deutsches Zentrum für Neurodegenerative Erkrankungen - DZNE, Helmholtz-Gemeinschaft Deutscher Forschungszentren; Universitätsklinikum Carl Gustav Carus Dresden; European Commission; European Research Council

Beyond its neurogenic ability, zebrafish radial glia play homeostatic roles at the level of neural circuits and brain barriers. Thus, the zebrafish radial glia can be considered as the ancestral homo...

Thanks to BPoD Medical Research Council for selecting our image from our last publication as the “beautiful picture of t...
02/21/2020

Thanks to BPoD Medical Research Council for selecting our image from our last publication as the “beautiful picture of the day” wıth nice commentary.
This image was generated by Prabesh Bhattarai.

New Nerves Please
Alzheimer’s disease is a fatal condition caused by the unstoppable death of nerve cells in the brain. Although current treatments can relieve the symptoms of the disease or slow its progress, there’s nothing that can stop or reverse the decline. Rather than trying to prevent nerve cell death, one controversial idea for treating Alzheimer’s involves producing new brain cells to replace those that have died. But it’s not clear whether this is technically possible, or whether generating new brain cells might cause more problems than it solves. In search of answers, scientists are studying zebrafish, whose simple brains are surprisingly similar to our own. These images show nerve cells (green) in the brain of a healthy fish (left) and animals that have been treated with various molecules. Two chemicals stimulate new cell production (pink spots, centre panels) while the third (right) does not, providing a useful model for further studies.

Written by Kat Arney

Image adapted from work by Prabesh Bhattarai and colleagues
German Center for Neurodegenerative Diseases (DZNE) within Helmholtz Association, Dresden, Germany
Image originally published with a Creative Commons Attribution 4.0 International (CC BY 4.0)
Published in PLOS Biology, January 2020

Originally on http://www.bpod.mrc.ac.uk/archive/2020/2/20
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Happy Valentine’s Day with the hearty brain of  !
02/14/2020

Happy Valentine’s Day with the hearty brain of !

Address

630 W 168th Street
New York, NY
10032

Website

https://www.neurology.columbia.edu/profile/caghan-kizil-phd

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