Research: Identifies glycosylation enzyme critical in brain formation

WASHINGTON: In a research from the University of California, Irvine, scientists found that the MGAT5 glycosylation enzyme plays a significant role in brain development. This finding may lead to new therapeutic applications for neural stem cells.

The final mature cells that develop from neural stem cells in the brain and spinal cord are neurons, astrocytes, and oligodendrocytes. Each performs unique and important roles. Signals are sent by neurons, modified by astrocytes, and maintained against deterioration by oligodendrocytes. Small sugar molecules are frequently added when any cells produce proteins or fats that end up on the cell surface. The researchers investigated if the internal process of glycosylation had any impact on how neural stem cells differentiate into mature brain cells.

The study, published in the journal Stem Cell Reports, found that during glycosylation, the MGAT5 enzyme significantly regulates the formation of neurons and astrocytes from neural stem cells. Neural stem cells that don’t have MGAT5 make more neurons and fewer astrocytes during the very early stages of brain development, altering its structure. These changes may contribute to later aberrant behaviour patterns, including abnormal social interactions and repetitive actions.

“Now that we know MGAT5 and glycosylation have a substantial impact on neuron and astrocyte formation, we have a better idea of how our nervous system develops,” said corresponding author Lisa Flanagan, professor of neurology in UCI’s School of Medicine. “We hope these findings will contribute to the use of neural stem cells for therapeutic purposes by providing new information about the factors regulating these cells.”

It was known that neural stem cells respond to the external signals they encounter during development. But it was not known whether neural stem cells could modify their responses to those signals. The team analyzed the role of glycosylation enzymes in brain maturation by comparing control mice to those whose neural stem cells did not have the MGAT5 enzyme. It found that neural stem cells use glycosylation to manage their reactions to external signals and regulate the development of mature brain cells.

“As we continue our work, we hope to determine which cell surface proteins and pathways controlled by glycosylation are critical for neuron and astrocyte formation,” Flanagan said. “This will give us better insight into the external signals significantly modified by neural stem cell glycosylation, which will, in turn, help to decode the complex processes that occur during brain development and expand the therapeutic use of neural stem cells.”