A role for myelin-associated peroxisomes in maintaining paranodal loops and axonal integrity
Abstract
Demyelinating diseases of the nervous system cause axon loss but the underlying mechanisms are not well understood. Here we show by confocal and electron microscopy that in myelin-forming glia peroxisomes are associated with myelin membranes. When peroxisome biogenesis is experimentally perturbed in Pex5 conditional mouse mutants, myelination by Schwann cells appears initially normal. However, in nerves of older mice paranodal loops become physically unstable and develop swellings filled with vesicles and electron-dense material. This novel model of a demyelinating neuropathy demonstrates that peroxisomes serve an important function in the peripheral myelin compartment, required for long-term axonal integrity.
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Peroxisomes are few in neuron perikarya or dendrites, rare within axons, and absent in synaptic terminals in the spinal cord except during early development.
“While mitochondria fill dendrites and axons, peroxisomes are few in neuron perikarya or dendrites, rare within axons [251,253,254,255,292,293], and absent in synaptic terminals in the spinal cord [255] except during early development [255].”
From Revisiting the Pathogenesis of X-Linked Adrenoleukodystrophy (2025) · cites this paper as [254]
In the brain, peroxisomes have been detected in all neural cell types: neurons, oligodendrocytes, astrocytes, microglia and endothelial cells.
“In the brain, peroxisomes appear as electron-dense single membrane-bound organelles that have been detected in all neural cell types, namely in neurons [13], oligodendrocytes [14,15] and astrocytes [13] and microglia and endothelial cells [16].”
From Peroxisomes in brain development and function (2016) · cites this paper as [14]
During early stages of murine peripheral nerve (sciatic nerve) myelination, peroxisomes appear diffusely distributed in the myelin sheath of Schwann cells, whereas at later stages they are enriched in the myelin loops of the paranodal region.
“During early stages of murine peripheral nerve (sciatic nerve) myelination, peroxisomes appear to be diffusely distributed in the myelin sheath of Schwann cells, whereas at later stages, peroxisomes were found to be enriched in the myelin loops of the paranodal region [14].”
From Peroxisomes in brain development and function (2016) · cites this paper as [14]
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References 30 · Cited by 52
- Authors
- Kassmann, C. M., Quintes, S., Rietdorf, J., Möbius, W., Sereda, M. W., Nientiedt, T., Saher, G., Baes, M., & Nave, K.-A.
- Affiliations
- Max Planck Institute of Experimental Medicine (DE)
- Friedrich Miescher Institute (CH)
- KU Leuven (BE)
- Corresponding author
- Nave, Klaus-Armin
- ORCID
- Venue
- FEBS Letters
- Publisher
- Wiley
- Published
- 2011-05-23
- Volume
- 585
- Issue
- 14
- Pages
- 2205-2211
- ISSN
- 0014-5793 (ISSN-L)
- OpenAlex
- W2136011227
- Cited by
- 52
- References
- 30
- Citations by year
- 2026: 5 · 2025: 3 · 2024: 2 · 2023: 3 · 2022: 2 · 2021: 4 · 2020: 7 · 2019: 1 · 2018: 3 · 2017: 2 · 2016: 4 · 2015: 2 · 2014: 1 · 2013: 9 · 2012: 3
- FWCI
- 1.84
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- FEBS Letters (publishedVersion)
- PubMed (publishedVersion)
- Max Planck Institute for Plasma Physics (submittedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Funders
- EU-FP6 (X-ALD, PEROXISOME)
- DFG (SFB/TR43)
- Oliver’s Army
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Hereditary Neurological Disorders
- Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Health Sciences › Medicine › Neurology › Peripheral Neuropathies and Disorders
- Keywords
- paranodal loops, axonal integrity, demyelinating neuropathy, Schwann cells, peroxisome biogenesis, PEX5, peripheral nerve myelin, axonal loss, myelination
- MeSH terms
- Peroxisome-Targeting Signal 1 Receptor, Animals, Axons, Mice, Inbred C57BL, Mice, Transgenic, Myelin Sheath, Nerve Fibers, Myelinated, Sciatic Nerve, Receptors, Cytoplasmic and Nuclear, Peroxisomes, Mice
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