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Folate receptor alpha (frα) and the developing brain: from molecular function to neurodevelopmental outcomes
Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik. Department of Cognitive Medicine, Ängelholm Hospital, Ängelholm, Sweden.ORCID-id: 0000-0002-0208-2877
Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi.ORCID-id: 0000-0003-0240-3690
Department of Physiology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Department of Clinical Medicine, Translational Neuropsychiatry Unit, Aarhus University, Aarhus, Denmark.
Department of Physiology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
2026 (Engelska)Ingår i: Molecular Neurobiology, ISSN 0893-7648, E-ISSN 1559-1182, Vol. 63, nr 1, artikel-id 522Artikel, forskningsöversikt (Refereegranskat) Published
Abstract [en]

Folate receptor alpha (FRα) is a high-affinity transporter responsible for delivering folate (vitamin B9) into the central nervous system (CNS), supporting the synthesis of nucleic acids, amino acids, lipids, and signaling molecules through one-carbon transfer pathways. Beyond its transport function, upon activation by folate, FRα modulates extracellular signaling, regulates membrane and cytosolic proteins, and gene transcription. Disruption of FRα, whether functional or structural, can impair CNS folate availability and lead to developmental abnormalities or neurological dysfunction, with the clinical consequences depending on the timing, severity, and presumably on the individual genetic background. Together, these insights position FRα as both a multifunctional regulator of cellular fate and a key molecular interface connecting folate metabolism, brain development, and neurobehavioral outcomes. This narrative review synthesizes the current state of knowledge on FRα, highlighting its roles in neuronal and glial differentiation, CNS maturation, and neural plasticity, while also examining the links between impaired FRα function and a spectrum of developmental and neuropsychiatric conditions. It also outlines the need for broader population-based studies to evaluate the diagnostic value of FRα autoantibodies and the therapeutic potential of folate supplementation.

Ort, förlag, år, upplaga, sidor
Springer Nature, 2026. Vol. 63, nr 1, artikel-id 522
Nyckelord [en]
Brain, Folate receptor alpha, Folate transport, Neurodevelopment
Nationell ämneskategori
Neurovetenskaper
Identifikatorer
URN: urn:nbn:se:umu:diva-252416DOI: 10.1007/s12035-026-05813-zISI: 001723044400001PubMedID: 41882276Scopus ID: 2-s2.0-105034373288OAI: oai:DiVA.org:umu-252416DiVA, id: diva2:2055693
Forskningsfinansiär
Knut och Alice Wallenbergs Stiftelse, KAW 2000.0200Vetenskapsrådet, 2023-02602Vetenskapsrådet, 2021-01872Hjärnfonden, FO2024-0049-TK-142Jane och Dan Olssons Stiftelse, pq2036gotTillgänglig från: 2026-04-27 Skapad: 2026-04-27 Senast uppdaterad: 2026-04-27Bibliografiskt granskad

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Egorova, OlgaDomellöf, Erik

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