Singapore Scientists Unlock Method to Stimulate Dormant Stem Cells in the Brain
In a recent research published in Science Advances, researchers from Duke-NUS Medical School and the Mechanobiology Institute (MBI) at the National University of Singapore (NUS) have identified a new pathway to activate dormant neural stem cells. This breakthrough could pave the way for innovative treatments for neurodevelopmental disorders like autism, learning disabilities, and cerebral palsy.
The findings revealed that astrocytes, a type of glial cell previously believed to offer only structural and nutritional support, play a crucial role in activating dormant neural stem cells in the brains of fruit flies.
Using super-resolution microscopy with 10 times magnification, the team of scientists examined the tiny fiber structures characteristic of dormant neural stem cells in fruit flies. These structures, about 1.5 µm in diameter (or 20 times smaller than a human hair), are protrusions from the cell body rich in actin filaments. A specific Formin protein can activate and assemble these filaments.
The scientists found that astrocytes release a signaling protein called Folded gastrulation (Fog), which triggers a series of events, including the activation of the Formin protein pathway to regulate actin filament movement. This process reactivates dormant neural stem cells, causing them to divide and generate new neurons that aid in brain repair and development.
The receptor protein GPCR in neural stem cells responds to Fog from astrocytes, activating the signaling pathway that controls actin filament formation. GPCRs play crucial roles in many cellular processes, and the GPCR protein family is a major drug target, with 34% of FDA-approved drugs targeting these proteins. Thus, understanding this signaling pathway could lead to new strategies for repurposing existing drugs to treat neurodevelopmental disorders.
This study is part of ongoing efforts to enhance our understanding of the fundamental mechanisms in the human brain, aiming to develop new therapeutic strategies, particularly for individuals with neurological conditions.
Reference: Kun-Yang Lin et al., Astrocytes control quiescent NSC reactivation via GPCR signaling–mediated F-actin remodeling.Sci. Adv.10,eadl4694(2024).DOI:10.1126/sciadv.adl4694
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