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Cited by 46Hereditary Neurological DisordersLysosomal Storage Disorders ResearchPeripheral Neuropathies and Disorders

Peroxisomal dysfunctions cause lysosomal storage and axonal Kv1 channel redistribution in peripheral neuropathy

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Kleinecke, Sandra, Richert, Sarah, de Hoz, Livia, Brügger, Britta, Kungl, Theresa, Asadollahi, Ebrahim, Quintes, Susanne, Blanz, Judith +10 more·2017·eLife
DOI 10.7554/elife.23332PMC PMC5417850
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Abstract

Impairment of peripheral nerve function is frequent in neurometabolic diseases, but mechanistically not well understood. Here, we report a novel disease mechanism and the finding that glial lipid metabolism is critical for axon function, independent of myelin itself. Surprisingly, nerves of Schwann cell-specific Pex5 mutant mice were unaltered regarding axon numbers, axonal calibers, and myelin sheath thickness by electron microscopy. In search for a molecular mechanism, we revealed enhanced abundance and internodal expression of axonal membrane proteins normally restricted to juxtaparanodal lipid-rafts. Gangliosides were altered and enriched within an expanded lysosomal compartment of paranodal loops. We revealed the same pathological features in a mouse model of human Adrenomyeloneuropathy, preceding disease-onset by one year. Thus, peroxisomal dysfunction causes secondary failure of local lysosomes, thereby impairing the turnover of gangliosides in myelin. This reveals a new aspect of axon-glia interactions, with Schwann cell lipid metabolism regulating the anchorage of juxtaparanodal Kv1-channels.

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  • Selective loss of functional peroxisomes in Schwann cells of CNP-Pex5 KO mice does not induce structural myelin deficits.

    “The selective loss of functional peroxisomes in Schwann cells of CNP-Pex5 KO mice does not induce structural myelin deficits [252].”

    From Revisiting the Pathogenesis of X-Linked Adrenoleukodystrophy (2025) · cites this paper as [252]

  • Conduction velocity in isolated sciatic nerves of CNP-Pex5 KO mice is diminished and compound action potentials are lower, despite unchanged axon numbers and sizes.

    “However, the conduction velocity in isolated sciatic nerves of these mice is diminished and compound action potentials are lower, despite unchanged axon numbers and sizes [252].”

    From Revisiting the Pathogenesis of X-Linked Adrenoleukodystrophy (2025) · cites this paper as [252]

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Authors
Kleinecke, S., Richert, S., de Hoz, L., Brügger, B., Kungl, T., Asadollahi, E., Quintes, S., Blanz, J., McGonigal, R., Naseri, K., Sereda, M. W., Sachsenheimer, T., Lüchtenborg, C., Möbius, W., Willison, H., Baes, M., Nave, K.-A., & Kassmann, C. M.
Affiliations
  • Max Planck Institute of Experimental Medicine (DE)
  • Department of Neurogenetics, Max Planck Institute of Experimental Medicine, Göttingen, Germany
  • Heidelberg University (DE)
  • Christian-Albrechts-Universität zu Kiel (DE)
  • University of Glasgow (GB)
  • Birjand University of Medical Sciences (IR)
  • KU Leuven (BE)
Corresponding author
Kassmann, Celia Michèle
ORCID
Venue
eLife
Publisher
eLife Sciences Publications, Ltd
Published
2017-05-04
Volume
6
ISSN
2050-084X (ISSN-L)
DOI
10.7554/elife.23332
PMC
PMC5417850
OpenAlex
W2611066600
Cited by
46
References
7
Citations by year
2026: 3 · 2025: 6 · 2024: 3 · 2023: 6 · 2022: 4 · 2021: 1 · 2020: 8 · 2019: 6 · 2018: 7 · 2017: 2
FWCI
3.08
Type
journal article
Language
en
Open access
Licence
Locations
  • eLife (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (acceptedVersion)
  • Lirias (submittedVersion, other-oa)
  • MPG.PuRe (Max Planck Society) (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
  • GoeScholar The Publication Server of the Georg-August-Universität Göttingen (Georg-August-Universität Göttingen) (submittedVersion, cc-by)
Funders
  • Deutsche Forschungsgemeinschaft (TR43, TRR83)
  • European Commission (ERC advanced grant - AxoGLIA, ERC advanced grant - MyeliNANO)
  • Olivers Army (Personal grant)
  • Myelin Project (Augusto Odone Young Investigator Award)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Hereditary Neurological Disorders
  • Health Sciences › Medicine › Physiology › Lysosomal Storage Disorders Research
  • Health Sciences › Medicine › Neurology › Peripheral Neuropathies and Disorders
Keywords
peroxisomal dysfunction, peripheral neuropathy, adrenomyeloneuropathy, Schwann cells, PEX5, lysosomal storage, gangliosides, Kv1 channels, lipid rafts, paranodal loops, axon-glia interaction, myelin, neurometabolic disorders
MeSH terms
Peroxisome-Targeting Signal 1 Receptor, Adrenoleukodystrophy, Animals, Axons, Disease Models, Animal, Humans, Lysosomes, Microscopy, Electron, Neuroglia, Peripheral Nervous System Diseases, Peroxisomes, Potassium Channels, Voltage-Gated, Lipid Metabolism, Mice

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