Folate receptor alpha is more than just a folate transporter

Until recently folate receptor alpha (FRα) has only been considered as a folate transporter. However, a novel role of FRα as a transcription factor was reported by our lab. More recently our lab showed a novel pleiotropic role of FRα: (a) direct transcriptional activation of Oct4, Sox2, and Klf4 genes; and (b) repression of biogenesis of miRNAs that target these genes or their effector molecules. These observations beg a question: "Can a simple molecule such as folate be used to manipulate the production and/or differentiation of endogenous neural stem cells (NSCs), which may hold promise for future therapies?" Conditions such as spinal cord injury, motor neuron diseases, Alzheimer's disease and multiple sclerosis may benefit from increasing stem cell pool and promoting specific pathways of differentiation. On the flip-side, these NSCs may also contribute to some CNS tumors therefore promoting differentiation could prove more beneficial. FRα may hold promises for both since it has the potential to remodel chromatin in a context dependent manner. In this commentary we discuss our previous data and new questions arising in the context of the new role for FRα.