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  Choroid plexus transcytosis and exosome shuttling deliver folate into brain parenchyma.

Grapp, M., Wrede, A., Schweizer, M., Hüwel, S., Galla, H., Snaidero, N., et al. (2013). Choroid plexus transcytosis and exosome shuttling deliver folate into brain parenchyma. Nature Communications, 4: 2123. doi:10.1038/ncomms3123.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0014-164F-1 Version Permalink: http://hdl.handle.net/11858/00-001M-0000-0028-3DA0-C
Genre: Journal Article

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 Creators:
Grapp, M., Author
Wrede, A., Author
Schweizer, M., Author
Hüwel, S., Author
Galla, H., Author
Snaidero, N., Author
Simons, M., Author
Bückers, J.1, Author              
Low, P. S., Author
Urlaub, H.2, Author              
Gärtner, J., Author
Steinfeld, R., Author
Affiliations:
1Department of NanoBiophotonics, MPI for biophysical chemistry, Max Planck Society, ou_578627              
2Research Group of Bioanalytical Mass Spectrometry, MPI for biophysical chemistry, Max Planck Society, ou_578613              

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 Abstract: Loss of folate receptor-α 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-α-positive intralumenal vesicles within multivesicular bodies and demonstrate the directional cotransport of human folate receptor-α, and labelled folate from the basolateral to the apical membrane in rat choroid plexus cells. Both the apical medium of folate receptor-α-transfected rat choroid plexus cells and human cerebrospinal fluid contain folate receptor-α-positive exosomes. Loss of folate receptor-α-expressing cerebrospinal fluid exosomes correlates with severely reduced 5-methyltetrahydrofolate concentration, corroborating the importance of the folate receptor-α-mediated folate transport in the cerebrospinal fluid. Intraventricular injections of folate receptor-α-positive and -negative exosomes into mouse brains demonstrate folate receptor-α-dependent delivery of exosomes into the brain parenchyma. Our results unravel a new pathway of folate receptor-α-dependent exosome-mediated folate delivery into the brain parenchyma and opens new avenues for cerebral drug targeting.

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Language(s): eng - English
 Dates: 2013-07-05
 Publication Status: Published online
 Pages: 13
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 Table of Contents: -
 Rev. Method: Peer
 Identifiers: DOI: 10.1038/ncomms3123
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Title: Nature Communications
Source Genre: Journal
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Pages: - Volume / Issue: 4 Sequence Number: 2123 Start / End Page: - Identifier: ISSN: 2041-1723