Regenerating brain cells could provide new therapeutics

  • Several recent publications have revealed that fruit flies can reactivate dormant neural stem cells in the brain to generate new neural cells important in brain function.

    Drosophila melanogaster, or fruit flies, have long been a model in scientific research to study genetics and development due to similarities to human processes. Because, despite obvious differences (wouldn’t it be great if we had wings?) humans and fruit flies aren’t too different. In fact, about 75% of human disease-causing genes are also found in fruit flies in similar forms, making them a useful tool to study disease and disease progression. Thus, human brain development can be studied using fruit flies as well.

    Neural stem cells in the brain can switch from dormant to active, allowing new neural cells to be generated. Most adult neural stems cells are quiescent, a dormant state, but can be reactivated on demand and when needed they can become activated again in response to stimuli. If too many are reactivated too quickly, the neural stem cell population becomes depleted prematurely. But failure in reactivation is linked to neurodegenerative and neurodevelopmental disorders such as Alzheimer’s disease. Little is still known about the process of reactivation.  

    A group of researchers at Duke-NUS Medical School in Singapore had a closer look at what goes on with neural stem cell reactivation, and they found that a protein complex called CRL4 is essential for the process. CRL4 has a few jobs: it downregulates a pathway that keeps neural stem cells dormant and forms a complex with a tumour suppressor called Warts. CRL4 targets and causes the degradation of Warts which triggers neural stem cell reactivation. CRL4 is a complex part of a much larger signalling pathway called the Hippo pathway that affects many parts of brain function including neural stem cell regulation.

    Another complex found in the brain involved in the Hippo pathway called STRIPAK plays a role in neural stem cell reactivation, according to scientists at the University of Plymouth. STRIPAK components can reduce quiescent stem cell numbers by switching off dormancy, thus can reactivate stem cells to increase the population of neural stem cells in the brain. Both CRL4 and STRIPAK play vital roles in maintaining and controlling neural stem cell populations.

    But why do we need neural stem cells? The reactivation of neural stem cells can stimulate production of new neural cells, which could help treat brain injury and brain damage from both trauma and disease. Diseases like Alzheimer’s and Parkinson’s disease result in loss of brain cells, and neural stem cell regeneration could produce more neural cells to compensate, providing a novel therapeutic treatment to help restore brain function. Not only could this therapeutic be a viable treatment, but reactivation of neural stem cells and knowledge of the signalling pathways involved could shed light on cancer of the brain prevention, sometimes caused by stem-like cells.

    However, these conclusions are based on the assumption that fruit fly and mammalian neural stem cells function through similar pathways with similar complexes involved. According to the researchers in Singapore, the protein complex CRL4 exists in mammalian brains, and further work needs to be done to elucidate whether the mechanisms work the same as in the fruit fly.

    With neurodegenerative diseases like Alzheimer’s and Parkinson’s on the rise as ageing populations increase, therapeutic treatments will be in higher demand, and regenerating dormant brain cells may help solve part of that problem.   

     

    Image by Peakpx.