Choroid plexus transcytosis and exosome shuttling deliver folate into brain parenchyma
2013 | Zeitschriftenartikel. Eine Publikation mit Affiliation zur Georg-August-Universität Göttingen.
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Dokumente & Medien
Details
- Autor(en)
- Grapp, Marcel; Wrede, Arne; Schweizer, Michaela; Huewel, Sabine; Galla, Hans-Joachim; Snaidero, Nicolas; Simons, Mikael ; Bueckers, Johanna ; Low, Philip S.; Urlaub, Henning ; Gärtner, Jutta ; Steinfeld, Robert
- Zusammenfassung
- Loss of folate receptor-alpha function is associated with cerebral folate transport deficiency and childhood-onset neurodegeneration. To clarify the mechanism of cerebral folate transport at the blood-cerebrospinal fluid barrier, we investigate the transport of 5-methyltetrahydrofolate in polarized cells. Here we identify folate receptor-alpha-positive intralumenal vesicles within multivesicular bodies and demonstrate the directional cotransport of human folate receptor-alpha, and labelled folate from the basolateral to the apical membrane in rat choroid plexus cells. Both the apical medium of folate receptor-alpha-transfected rat choroid plexus cells and human cerebrospinal fluid contain folate receptor-alpha-positive exosomes. Loss of folate receptor-alpha-expressing cerebrospinal fluid exosomes correlates with severely reduced 5-methyltetrahydrofolate concentration, corroborating the importance of the folate receptor-alpha-mediated folate transport in the cerebrospinal fluid. Intraventricular injections of folate receptor-alpha-positive and -negative exosomes into mouse brains demonstrate folate receptor-alpha-dependent delivery of exosomes into the brain parenchyma. Our results unravel a new pathway of folate receptor-alpha-dependent exosome-mediated folate delivery into the brain parenchyma and opens new avenues for cerebral drug targeting.
- Erscheinungsdatum
- 2013
- Zeitschrift
- Nature Communications
- ISSN
- 2041-1723