Neopterin as a potential cytoprotective brain molecule

• Neopterin is widely recognized as a sensitive biomarker of immune system activation.
• Neopterin is a byproduct of the tetrahydrobiopterin de novo pathway.
• Neopterin is released by myeloid cells.
• It seems that neopterin is also synthesized and secreted by nerve cells.
• Released neopterin induce extra and intracellular effects under stressful conditions.

Neopterin, a byproduct of the tetrahydrobiopterin de novo pathway, is found in increased levels in cerebrospinal fluid and plasma and significantly increases upon damage, infection or during immune system activation. The production of this compound seems almost restricted to the monocyte/macrophage linage cells, in response to interferon-γ stimulation. However, it is unclear whether and which nervous cells are able to synthesize neopterin, respond to any stressor applied extracellularly, or even the role of the compound in the central nervous system. Here we propose a potential cytoprotective role of neopterin in the brain, and show evidence that cultured rat astrocytes are responsive to the molecule; the pterin elicited increased hemeoxygenase-1 cellular content and decreased oxidative stress induced by mitochondrial dysfunction. Further studies are needed to clarify neopterin's cytoprotective effects in the central nervous system, and its potential role in different neuroinflammatory diseases.