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

Fledrich, Robert; Abdelaal, Tamer A. M.; Rasch, Lennart; Bansal, V.; Schütza, Vlad; Brügger, B.; Lüchtenborg, C.; Prukop, Thomas; Stenzel, Jan; Rahman, R.U.; Hermes, Doris; Ewers, David; Möbius, Wiebke; Ruhwedel, Torben; Katona, I.; Weis, J.; Klein, D.; Martini, R.; Brück, W.; Müller, W.C.; Bonn, S.; Bechmann, I.; Nave, Klaus-Armin; Stassart, Ruth M.; Sereda, Michael Werner

doi:10.1038/s41467-018-05420-0

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

MPG-Autoren

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Fledrich, Robert
Molecular and translational neurology, Neurogenetics, Max Planck Institute of Experimental Medicine, Max Planck Society;

/persons/resource/persons182057

Abdelaal, Tamer A. M.
Neurogenetics, Max Planck Institute of Experimental Medicine, Max Planck Society;

/persons/resource/persons182363

Rasch, Lennart
Neurogenetics, Max Planck Institute of Experimental Medicine, Max Planck Society;

/persons/resource/persons224786

Schütza, Vlad
Neurogenetics, Max Planck Institute of Experimental Medicine, Max Planck Society;

/persons/resource/persons182356

Prukop, Thomas
Neurogenetics, Max Planck Institute of Experimental Medicine, Max Planck Society;

/persons/resource/persons224788

Stenzel, Jan
Neurogenetics, Max Planck Institute of Experimental Medicine, Max Planck Society;

/persons/resource/persons224792

Hermes, Doris
Neurogenetics, Max Planck Institute of Experimental Medicine, Max Planck Society;

/persons/resource/persons224794

Ewers, David
Neurogenetics, Max Planck Institute of Experimental Medicine, Max Planck Society;

/persons/resource/persons182306

Möbius, Wiebke
Electron microscopy, Neurogenetics, Max Planck Institute of Experimental Medicine, Max Planck Society;

/persons/resource/persons182382

Ruhwedel, Torben
Electron microscopy, Neurogenetics, Max Planck Institute of Experimental Medicine, Max Planck Society;

/persons/resource/persons182320

Nave, Klaus-Armin
Neurogenetics, Max Planck Institute of Experimental Medicine, Max Planck Society;

/persons/resource/persons182427

Stassart, Ruth M.
Neurogenetics, Max Planck Institute of Experimental Medicine, Max Planck Society;

/persons/resource/persons182406

Sereda, Michael Werner
Molecular and translational neurology, Neurogenetics, Max Planck Institute of Experimental Medicine, Max Planck Society;

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Zitation

Fledrich, R., Abdelaal, T. A. M., Rasch, L., Bansal, V., Schütza, V., Brügger, B., et al. (2018). Targeting myelin lipid metabolism as a potential therapeutic strategy in a model of CMT1A neuropathy. Nature Communications, 9: 3025. doi:10.1038/s41467-018-05420-0.

Zitierlink: https://hdl.handle.net/21.11116/0000-0001-E40B-2

Zusammenfassung

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.