Neuroscientists have discovered a mechanism that governs the reactivation of neural stem cells, which are essential for the repair and regeneration of brain cells. This research presents promising opportunities to enhance our understanding and treatment of prevalent neurodegenerative disorders, including Alzheimer’s and Parkinson’s disease.
An international research team, led by Duke-NUS Medical School, has identified a key mechanism responsible for reactivating neural stem cells, which play a vital role in restoring and regenerating brain cells. Their findings, published in Nature Communications, open exciting avenues for improving our understanding and treatment of common neurodegenerative diseases like Alzheimer’s and Parkinson’s disease.
Neural stem cells serve as the original source of the brain’s main functional cells. Once the brain develops, these cells usually enter a resting phase to conserve energy. They awaken only when necessary, such as during recovery from an injury or through physical activity. However, as we age, fewer of these stem cells can be activated, leading to various neurological issues. Grasping how this reactivation occurs is crucial for crafting treatments for multiple neurological disorders.
The study revealed that a particular group of proteins is vital in “reviving” dormant neural stem cells through a process known as SUMOylation.
During SUMOylation, a small protein called SUMO (small ubiquitin-like modifier) attaches to target proteins within cells, modifying their activity or function. The researchers identified that these SUMO-tagged proteins activate the reactivation of neural stem cells, enabling them to aid in brain growth and repair. In contrast, the absence of SUMO proteins led to fruit flies exhibiting a phenotype similar to microcephaly. This research marks the first instance of identifying the SUMO protein family’s specific contribution to the reactivation of neural stem cells.
Dr. Gao Yang, a research fellow from Duke-NUS’ Neuroscience and Behavioral Disorders Program and the lead author of the study, commented:
“For the first time, we’ve shown that the SUMO protein family is crucial for neural stem cell reactivation and overall brain development. Moreover, our research indicates that the lack of these proteins can impede normal neuronal development, leading to fruit flies having undersized brains characteristic of microcephaly.”
Exploring SUMOylation further, the researchers found that it regulates a significant protein in a well-known pathway called Hippo. The Hippo pathway is critical for various cellular activities, including cell growth, death, and organ size, yet little is known about its regulators in the brain.
When the Hippo pathway’s main protein, Warts, is modified by SUMO, it becomes less capable of restricting cell growth and allows neural stem cells to activate, proliferate, and form new neurons that support brain function.
Professor Wang Hongyan, Acting Programme Director of the Neuroscience and Behavioral Disorders Research Program and senior author of the study, remarked:
“As SUMO proteins and the Hippo pathway are highly conserved across species, our findings have implications beyond fruit flies. They are significant for understanding human biology. Malfunctions in the SUMOylation process and the Hippo pathway are associated with several human diseases, including cancer and neurodegenerative conditions like Alzheimer’s and Parkinson’s disease. Our new understanding of SUMOylation’s role in the brain paves the way for potential interventions that leverage the body’s inherent regenerative capabilities.”
Prof. Wang and her colleagues have previously demonstrated that fruit fly neural stem cells serve as a valuable model for investigating dormancy, reactivation, and neuronal regeneration.
Professor Patrick Tan, Senior Vice-Dean for Research at Duke-NUS, added:
“This finding enhances our comprehension of cellular functions and regulation, guiding the way for innovative regenerative therapies for neurodegenerative diseases. Furthermore, it reveals new possibilities for treating neurological conditions like microcephaly. As research advances, we get closer to discovering effective strategies to assist individuals with these disorders, thereby improving their quality of life.”
