Neuron-like cells created from a readily available cell line have allowed researchers to investigate how the human brain makes a metabolic building block essential for the survival of all living organisms. A team led by researchers from Penn State optimized a new method to create the synthetic neurons, which they used to investigate a core enzyme involved in the synthesis of purines — a component of DNA that is involved in many other cellular and metabolic processes — and how the enzyme might change during infection by herpes simplex virus. An early version of the paper describing the enzyme appears online in Jan. 2018 in the Journal of Neurochemistry, and a paper describing the neuron-like cells appeared in Journal of Virology (“Expression of the purine biosynthetic enzyme phosphoribosyl formylglycinamidine synthase (FGAMS) in neurons”).
“These newly developed neuron-like cells allowed us to investigate purine formation in a specialized cell type for the first time,” said Moriah Szpara, assistant professor of biochemistry and molecular biology at Penn State and senior author of both papers. “We were interested in neurons because they require a lot of energy and therefore need to produce purines efficiently. We were also curious how the synthesis process might be affected by infection with herpes simplex virus, an energetically demanding virus that takes up residence in neurons.”
When demand for purines is high in a cell, a complex composed of many enzymes called the purinosome forms to enable faster production of these important chemicals. The researchers investigated an enzyme called FGAMS, a core component of the purinosome. To better understand the role of FGAMS in purine production, they looked at where and how much of the enzyme is expressed in rodent brain slices, rodent neurons, human non-neuronal cells, and the human neuron-like cells cultivated with the new technique.