Exploring the Regulation of Low Affinity Folate Transporters in the Brain

Professor Reina Bendayan at the Leslie Dan Faculty of Pharmacy is the recipient of a five-year NSERC grant to explore the regulation of low affinity folate transporters in the brain.

Folates are water soluble vitamins that play a critical role in tissue development, function, and repair. Humans must obtain folate from their diet since they cannot synthesize it from other nutrients.

Folate deficiency is a major global dietary health problem, affecting tissues such as bone marrow, intestine, and brain development.

Folates cross biological membranes poorly, and therefore require specific membrane carriers or receptors for intestinal uptake and gain access to vital organs like the brain. Folate receptor alpha constitutes a major transport pathway in the brain. Folate transport is critical for the maintenance of normal brain function, yet mutations in folate receptors alpha and the presence of antibodies against this receptor can cause severe folate deficiency.

To date, folate transport in the brain has been largely investigated through folate receptor alpha. However, at least two other transport systems for folates exist – the proton-coupled folate transporter and the reduced folate carrier – though they have a lower affinity for folates. At this time, the role that these transporters play in the overall brain folate uptake is unclear.

Through this grant, Professor Bendayan will explore the contribution of these two low affinity folate transporters in folate uptake at the blood-brain barrier. This research will investigate whether, in the context of folate receptor alpha mutations or the presence of folate receptor alpha antibodies that render folate transport ineffective, the low affinity folate transporters have the potential to play a significant role in brain folate uptake.

Ultimately, Professor Bendayan hopes that this research could uncover novel strategies for the treatment of brain disorders caused by folic acid deficiency.