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Targeting myelin lipid metabolism as a potential therapeutic strategy in a model of CMT1A neuropathy

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Targeting myelin lipid metabolism as a potential therapeutic strategy in a model of CMT1A neuropathy. / Fledrich, R; Abdelaal, T; Rasch, L; Bansal, V; Schütza, V; Brügger, B; Lüchtenborg, C; Prukop, T; Stenzel, J; Rahman, R U; Hermes, D; Ewers, D; Möbius, W; Ruhwedel, T; Katona, I; Weis, J; Klein, D; Martini, R; Brück, W; Müller, W C; Bonn, S; Bechmann, I; Nave, K A; Stassart, R M; Sereda, M W.

in: NAT COMMUN, Jahrgang 9, Nr. 1, 02.08.2018, S. 3025.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Fledrich, R, Abdelaal, T, Rasch, L, Bansal, V, Schütza, V, Brügger, B, Lüchtenborg, C, Prukop, T, Stenzel, J, Rahman, RU, Hermes, D, Ewers, D, Möbius, W, Ruhwedel, T, Katona, I, Weis, J, Klein, D, Martini, R, Brück, W, Müller, WC, Bonn, S, Bechmann, I, Nave, KA, Stassart, RM & Sereda, MW 2018, 'Targeting myelin lipid metabolism as a potential therapeutic strategy in a model of CMT1A neuropathy', NAT COMMUN, Jg. 9, Nr. 1, S. 3025. https://doi.org/10.1038/s41467-018-05420-0

APA

Fledrich, R., Abdelaal, T., Rasch, L., Bansal, V., Schütza, V., Brügger, B., Lüchtenborg, C., Prukop, T., Stenzel, J., Rahman, R. U., Hermes, D., Ewers, D., Möbius, W., Ruhwedel, T., Katona, I., Weis, J., Klein, D., Martini, R., Brück, W., ... Sereda, M. W. (2018). Targeting myelin lipid metabolism as a potential therapeutic strategy in a model of CMT1A neuropathy. NAT COMMUN, 9(1), 3025. https://doi.org/10.1038/s41467-018-05420-0

Vancouver

Fledrich R, Abdelaal T, Rasch L, Bansal V, Schütza V, Brügger B et al. Targeting myelin lipid metabolism as a potential therapeutic strategy in a model of CMT1A neuropathy. NAT COMMUN. 2018 Aug 2;9(1):3025. https://doi.org/10.1038/s41467-018-05420-0

Bibtex

@article{ae30ea81fb044af390e28a1ac10cee1c,
title = "Targeting myelin lipid metabolism as a potential therapeutic strategy in a model of CMT1A neuropathy",
abstract = "In patients with Charcot-Marie-Tooth disease 1A (CMT1A), peripheral nerves display aberrant myelination during postnatal development, followed by slowly progressive demyelination and axonal loss during adult life. Here, we show that myelinating Schwann cells in a rat model of CMT1A exhibit a developmental defect that includes reduced transcription of genes required for myelin lipid biosynthesis. Consequently, lipid incorporation into myelin is reduced, leading to an overall distorted stoichiometry of myelin proteins and lipids with ultrastructural changes of the myelin sheath. Substitution of phosphatidylcholine and phosphatidylethanolamine in the diet is sufficient to overcome the myelination deficit of affected Schwann cells in vivo. This treatment rescues the number of myelinated axons in the peripheral nerves of the CMT rats and leads to a marked amelioration of neuropathic symptoms. We propose that lipid supplementation is an easily translatable potential therapeutic approach in CMT1A and possibly other dysmyelinating neuropathies.",
keywords = "Animals, Axons, Charcot-Marie-Tooth Disease, Dietary Fats, Lipid Metabolism, Lipids, Myelin Sheath, Phospholipids, Rats, Transgenic, Schwann Cells, Journal Article, Research Support, Non-U.S. Gov't",
author = "R Fledrich and T Abdelaal and L Rasch and V Bansal and V Sch{\"u}tza and B Br{\"u}gger and C L{\"u}chtenborg and T Prukop and J Stenzel and Rahman, {R U} and D Hermes and D Ewers and W M{\"o}bius and T Ruhwedel and I Katona and J Weis and D Klein and R Martini and W Br{\"u}ck and M{\"u}ller, {W C} and S Bonn and I Bechmann and Nave, {K A} and Stassart, {R M} and Sereda, {M W}",
year = "2018",
month = aug,
day = "2",
doi = "10.1038/s41467-018-05420-0",
language = "English",
volume = "9",
pages = "3025",
journal = "NAT COMMUN",
issn = "2041-1723",
publisher = "NATURE PUBLISHING GROUP",
number = "1",

}

RIS

TY - JOUR

T1 - Targeting myelin lipid metabolism as a potential therapeutic strategy in a model of CMT1A neuropathy

AU - Fledrich, R

AU - Abdelaal, T

AU - Rasch, L

AU - Bansal, V

AU - Schütza, V

AU - Brügger, B

AU - Lüchtenborg, C

AU - Prukop, T

AU - Stenzel, J

AU - Rahman, R U

AU - Hermes, D

AU - Ewers, D

AU - Möbius, W

AU - Ruhwedel, T

AU - Katona, I

AU - Weis, J

AU - Klein, D

AU - Martini, R

AU - Brück, W

AU - Müller, W C

AU - Bonn, S

AU - Bechmann, I

AU - Nave, K A

AU - Stassart, R M

AU - Sereda, M W

PY - 2018/8/2

Y1 - 2018/8/2

N2 - In patients with Charcot-Marie-Tooth disease 1A (CMT1A), peripheral nerves display aberrant myelination during postnatal development, followed by slowly progressive demyelination and axonal loss during adult life. Here, we show that myelinating Schwann cells in a rat model of CMT1A exhibit a developmental defect that includes reduced transcription of genes required for myelin lipid biosynthesis. Consequently, lipid incorporation into myelin is reduced, leading to an overall distorted stoichiometry of myelin proteins and lipids with ultrastructural changes of the myelin sheath. Substitution of phosphatidylcholine and phosphatidylethanolamine in the diet is sufficient to overcome the myelination deficit of affected Schwann cells in vivo. This treatment rescues the number of myelinated axons in the peripheral nerves of the CMT rats and leads to a marked amelioration of neuropathic symptoms. We propose that lipid supplementation is an easily translatable potential therapeutic approach in CMT1A and possibly other dysmyelinating neuropathies.

AB - In patients with Charcot-Marie-Tooth disease 1A (CMT1A), peripheral nerves display aberrant myelination during postnatal development, followed by slowly progressive demyelination and axonal loss during adult life. Here, we show that myelinating Schwann cells in a rat model of CMT1A exhibit a developmental defect that includes reduced transcription of genes required for myelin lipid biosynthesis. Consequently, lipid incorporation into myelin is reduced, leading to an overall distorted stoichiometry of myelin proteins and lipids with ultrastructural changes of the myelin sheath. Substitution of phosphatidylcholine and phosphatidylethanolamine in the diet is sufficient to overcome the myelination deficit of affected Schwann cells in vivo. This treatment rescues the number of myelinated axons in the peripheral nerves of the CMT rats and leads to a marked amelioration of neuropathic symptoms. We propose that lipid supplementation is an easily translatable potential therapeutic approach in CMT1A and possibly other dysmyelinating neuropathies.

KW - Animals

KW - Axons

KW - Charcot-Marie-Tooth Disease

KW - Dietary Fats

KW - Lipid Metabolism

KW - Lipids

KW - Myelin Sheath

KW - Phospholipids

KW - Rats, Transgenic

KW - Schwann Cells

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1038/s41467-018-05420-0

DO - 10.1038/s41467-018-05420-0

M3 - SCORING: Journal article

C2 - 30072689

VL - 9

SP - 3025

JO - NAT COMMUN

JF - NAT COMMUN

SN - 2041-1723

IS - 1

ER -