Uncovering the mechanisms for neuronal stem cell activation
A team of neuroscientists has elucidated the mechanisms involved in neuronal stem cell activation, which may be key in developing treatments for neurodegenerative diseases.
A research group, led by neuroscientists at Duke-NUS Medical School (Singapore), has recently uncovered the mechanism governing the activation of neural stem cells (NSCs), which play a crucial role in neuron regeneration. Understanding this process is key to developing new treatments for neurological diseases.
NSCs are essential for the development of the nervous system, including the brain. In adult brains, NSCs generally exist in a dormant state but can be reactivated by external signals such as injury or exercise. As humans age, the pathway that regulates NSC activation and neuronal development, known as the Hippo pathway, can become dysregulated and prevent neural regeneration even when required. This can advance the progression of various neurological disorders, including Alzheimer’s disease.
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To develop new treatments for these disorders, the research team has sought to understand the processes behind NSC activation, hoping to modify the Hippo pathway to promote neuronal regeneration. Through various gene expression analyses in fruit flies, the team was able to pinpoint a process known as ‘SUMOylation’ as crucial for NSC activation.
During SUMOylation, cellular proteins are tagged by a small ubiquitin-related modifier (SUMO) peptide. This incites a rapid change in protein function which, in the case of NSCs, confers alteration of the cell from a dormant to an active state. In genetically altered fruit flies that did not express SUMO proteins, the researchers observed a microcephaly-like phenotype – confirming SUMOylation’s key role in neuronal development. Additionally, alterations to Hippo by SUMO caused the pathway to become less effective at limiting NSC activation, prompting NSC growth, division and neuron formation.
Both SUMOylation and the Hippo pathway are evolutionarily conserved, meaning they operate similarly in humans and fruit flies. The researchers hope to apply their new understanding of these processes to develop human therapeutics for neurological diseases. Wang Hongyan, senior author of the study, explained that, “New insights into the role of SUMOylation in the brain opens exciting new opportunities for interventions that could lead to targeted therapies that harness the body’s own regenerative powers.”
