Preclinical Development – Biomolecular
2019 PharmSci 360
Folates are essential for brain development and function. Folate transport in mammalian tissues is mediated by three major systems, i.e., reduced folate carrier (RFC), proton-coupled folate transporter (PCFT) and folate receptor alpha (FRα). Brain folate uptake primarily occurs at the choroid plexus through the concerted actions of FRα and PCFT. Inactivating mutations on FRα or PCFT can cause cerebral folate deficiency, resulting in childhood neurodegeneration. Thus, identifying alternative routes for brain folate delivery could lead to therapeutic benefits. This presentation will address the role of RFC in folate uptake at the blood-brain barrier (BBB) and its potential regulation by ligand-activated nuclear receptors such as the vitamin D receptor (VDR), as well as highlight the potential therapeutic role of Vitamin D in the treatment of cerebral folate deficiency.