Summary: SUMO proteins play a vital part in activating inert neural stem cells, important for head repair and rejuvenation. This getting, centered on a procedure called SUMOylation, reveals how neural stem cells can remain “woken up” to help in mental treatment, offering possible treatments for neurological conditions.
By altering the Hippo pathway, which is essential for cell growth and repair, SUMO proteins influence neural stem cell reactivation. The study’s insights lay foundational groundwork for developing regenerative therapies to combat conditions like Alzheimer’s and Parkinson’s disease.
Key Facts:
- SUMO proteins activate dormant neural stem cells, aiding brain repair.
- By modifying the Hippo pathway, SUMOylation regulates neural stem cells.
- Findings provide a foundation for regenerative therapies for neurodegenerative diseases.
Source: Duke NUS Medical School
An international team of neuroscientists, led by Duke-NUS Medical School, have uncovered a mechanism that controls the reactivation of neural stem cells, which are crucial for repairing and regenerating brain cells.
The research, published in , Nature Communications, offers exciting potential for advancing our understanding and treatment of common neurodegenerative diseases like Alzheimer’s and Parkinson’s disease.
The primary functional cells in the brain are neural stem cells. Neuronal stem cells typically go into a dormant state, conserving energy and resources after the brain’s initial development. Only when the brain needs them, such as after an accident or during physical activity, do they re-awaken.
However, with age, fewer neural stem cells can be roused from their dormant state, leading to various neurological conditions. It is crucial to develop treatments for various neurological conditions to understand how this reactivation is controlled.
The team’s discovery in this study led to the discovery that a particular group of proteins, known as SUMOylation, are essential for “waking up” dormant neural stem cells.
In SUMOylation, a small protein named SUMO ( small ubiquitin-like modifier ) tags target proteins inside a cell to influence their activity and/or function. These SUMO-tagged proteins, the researchers found, trigger the reactivation of neural stem cells, allowing them to contribute to brain development and repair.
Conversely, without SUMO proteins present, the fruit flies produced a microcephaly-like phenotype. This is the first study to specifically identify the SUMO protein family’s role in neural stem cell reactivation.
Dr Gao Yang, a research fellow with Duke-NUS ‘ Neuroscience and Behavioural Disorders Programme and the study’s first author, remarked:
We have demonstrated for the first time that the SUMO protein family is essential to the development of brains as a whole. Going a step further, we also showed that when these proteins are absent, normal neuronal development is hampered, with fruit flies developing undersized brains characteristic of microcephaly”.
Delving deeper into the effects of SUMOylation, the researchers determined that it regulates a key protein in another well-known pathway, called Hippo. Although it is well known that the Hippo pathway regulates cellular processes like cell proliferation, cell death, and organ size, there are only a few brain-specific regulators that are known.
When modified by SUMO, the Hippo pathway’s central protein Warts, which limits cell growth and prevents the reactivation of neural stem cells, becomes less effective. This enables the division of neural stem cells into new neurons that aid in brain function.
Senior author of the study, Professor Wang Hongyan, Acting Programme Director of the Neuroscience and Behavioural Disorders Research Programme, and Professor Wang Hongyan, said:
Our findings are not just applicable to fruit flies because SUMO proteins and the Hippo pathway are highly conserved in humans. They’re also important for understanding human biology.
” Disruptions in the SUMOylation process and Hippo pathway are linked to various illnesses in humans, including cancer and neurodegenerative diseases, like Alzheimer’s and Parkinson’s disease.
” Our recent investigations into the brain’s role provide exciting new avenues for therapeutics that can harness the body’s own regenerative powers,” says Dr. S. A.
Prof Wang and her team had previously demonstrated that fruit fly neural stem cells are  , an excellent model , for unravelling the mysteries of dormancy, reactivation and neuronal regeneration.
Professor Patrick Tan, Senior Vice-Dean for Research at Duke-NUS, commented:
This discovery advances our understanding of how cells function and how they are controlled, leading to the creation of novel regenerative treatments for neurodegenerative diseases.
It opens new avenues for developing treatments for neurological conditions like microcephaly at the same time. As research develops, we are closer to finding effective ways to improve the quality of life for those who suffer from these disorders.
Duke-NUS is a leader in medical research and education, and its mission is to advance patient care through cutting-edge scientific research.
In order to develop new therapeutic strategies, especially for those with neurological conditions, the study is a part of its ongoing efforts to better understand the fundamental mechanisms at play in the human brain.
About this news about neuroscience and genetics
Author: Brandon Raeburn
Source: Duke NUS Medical School
Contact: Brandon Raeburn – Duke NUS Medical School
Image: The image is credited to Neuroscience News
Original Research: Open access.
Gao Yang and colleagues ‘ work” Sumoylation of Warts Kinase Promotes Neural Stem Cell Reactivation.” Nature Communications
Abstract
Neural Stem Cell Reactivation is Promoted by the MOYlation of Warts Kinase.
Adult neurogenesis and homeostasis depend on a delicate balance between neural stem cell ( NSC ) quiescence and proliferation.
Small ubiquitin-related modifier ( SUMO ) -dependent post-translational modifications cause rapid and reversible changes in protein functions. However, the role of the SUMO pathway during NSC reactivation and brain development is not established.
We demonstrate here that the main SUMO pathway components play a significant role in Drosophila‘s NSC reactivation and brain development.
Depletion of SUMO/Smt3 or SUMO conjugating enzyme Ubc9 results in notable defects in NSC reactivation and brain development, while their overexpression leads to premature NSC reactivation.
Smt3 protein levels increase with NSC reactivation, which is promoted by the Ser/Thr kinase Akt. Warts/Lats, the core protein kinase of the Hippo pathway, can undergo SUMO- and Ubc9-dependent SUMOylation at Lys766.
This modification attenuates Wts phosphorylation by Hippo, leading to the inhibition of the Hippo pathway, and consequently, initiation of NSC reactivation. Additionally, inhibiting the Hippo pathway effectively corrects the NSC reactivation defects brought on by SUMO pathway inhibition.
Overall, our study uncovered an important role for the SUMO-Hippo pathway during , Drosophila , NSC reactivation and brain development.
