Duke-NUS Medical School Discovered Breakthrough Treatment for Neurodevelopmental Disorders
Researchers at Duke-NUS Medical School and the Mechanobiology Institute (MBI) at the National University of Singapore (NUS) have uncovered a novel pathway that can awaken dormant neural stem cells, paving the way for potential new therapies for neurodevelopmental disorders such as autism, learning disabilities, and cerebral palsy.
In the adult mammalian brain, neural stem cells, which are derived from the nervous system and have the potential to develop into various types of brain cells, generally remain dormant until they receive specific activation signals. Once activated, these stem cells generate new neurons, aiding in brain growth and repair.
Failures in the activation of neural stem cells have been linked to cognitive decline associated with ageing and neurodevelopmental disorders like microcephaly, a condition where a baby’s brain does not develop properly, resulting in a significantly smaller head size.
Neurodevelopmental disorders impact approximately five per cent of children and adolescents globally, leading to challenges in cognition, communication, adaptive behaviour, and motor skills.
The research team employed super-resolution microscopy, which magnifies structures by ten times, to study the minute fibre structures characteristic of dormant neural stem cells in fruit flies. These delicate structures, measuring about 1.5 µm in diameter (20 times smaller than a human hair), protrude from the cell body and are rich in actin, a protein filament. The assembly of these filaments can be triggered by a specific Formin protein.
The scientists discovered that astrocytes, a type of brain cell, release a signalling protein called Folded gastrulation (Fog), initiating a chain reaction that activates the Formin protein pathway, which controls the movement of actin filaments. This process ultimately rouses the neural stem cells from dormancy, leading them to divide and produce new neurons that contribute to brain repair and development.
The receptor protein GPCR, found in neural stem cells, responds to the Fog protein secreted by astrocytes, activating a signalling pathway that governs the formation of actin filaments in these cells. GPCRs play crucial roles in fundamental cellular processes.
This discovery highlights the significant role of astrocytes in reactivating neural stem cells and offers new insights into brain cell development. It also opens up promising possibilities for developing therapies targeting neurological disorders, brain ageing, and injuries.
