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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 comparative 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.
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