Clinical Implications of Folate Transport in the Central Nervous System. (May 2020)

• Record Type: Journal Article
• Authors: Alam, Camille; Kondo, Misaki; O'Connor, Deborah L.; Bendayan, Reina
• Is Part Of: Trends in pharmacological sciences. Volume 41:Number 5(2020)
• Page Start: 349
• Page End: 361
• Publication Date: 2020-05
• Subjects: folate receptor -- reduced folate carrier -- proton-coupled folate transporter -- central nervous system -- folate deficiency -- folate supplementation; Pharmacology -- Periodicals; Pharmacology -- trends -- Periodicals; Pharmacologie -- Périodiques; Pharmacology; Electronic journals; Periodicals; 615.1
• DOI: 10.1016/j.tips.2020.02.004
• Languages: English
• ISSNs: 0165-6147

Abstract

Abstract : Folates are essential for key biosynthetic processes in mammalian cells and play a crucial role in the maintenance of central nervous system homeostasis. Mammals lack the metabolic capacity for folate biosynthesis; hence, folate requirements are largely met through dietary sources. To date, three major folate transport pathways have been characterized: the folate receptors (FRs), reduced folate carrier (RFC), and proton-coupled folate transporter (PCFT). This article reviews current knowledge on the role of folate transport systems in mediating folate delivery to vital tissues, particularly the brain, and how these pathways are modulated by various regulatory mechanisms. We will also briefly highlight the clinical significance of cerebral folate transport in relation to neurodevelopmental disorders associated with folate deficiency. Highlights: Folate transport in mammalian brain is mediated by three major pathways: folate receptor alpha (FRα; FOLR1 ), proton-coupled folate transporter (PCFT; SLC46A1 ), and reduced folate carrier (RFC; SLC19A1 ). Folate delivery to the brain primarily occurs at the choroid plexus through FRα and PCFT. Loss-of-function mutations in these transport systems have been implicated in a number of childhood neurological disorders, including cerebral folate deficiency, hereditary folate malabsorption, and autism. Currently, there is limited knowledge on the contribution of other brain regions (i.e., blood–brain barrier) to overall brain folate uptake. Increasing folate permeability into the brain or finding alternative routes for effective brain folate transport could lead to significant therapeutic benefits.