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Peroxisomal integrity in myeloid cells is required for myelin debris clearance and remyelination

GSE272138 Mus musculus Expression profiling by high throughput sequencing 8 samples Submitted 2025/11/13 Platform GPL24247
Summary
During demyelination myeloid cells remove myelin debris and promote remyelination. Dysfunctional myeloid cells are associated with peroxisomal leukodystrophies, yet the role of peroxisomes in myeloid cells responding to demyelination remains unknown. The impact of dysfunctional peroxisomes in demyelination-responding myeloid cells was interrogated in Abcd1 and Pex5 knockout mice using the cuprizone model for myelin damage. Abcd1 loss did not affect the demyelination response in myeloid cells, however, Pex5 deficiency impaired remyelination and significantly undermined myelin debris clearance. Molecular analysis in Pex5 depleted macrophages revealed repressed APOE activity and attenuated expression of the sterol exporter pathway integral to myelin debris metabolism, which was associated with an aggravated foamy macrophage phenotype in myelin engulfing myeloid cells. In summary, we report a critical contribution of peroxisomes to myelin debris clearance, myelin lipid processing, and pro-remyelinating properties in myeloid cells.
Published in
Peroxisomal integrity in demyelination-associated microglia enables cellular debris clearance and myelin renewal in mice
Barnes-Vélez JA, Zhang X, Peña Señeriz YL et al. · The Journal of clinical investigation 2026 · PMID 41196656 · doi:10.1172/JCI179985
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Also filed as BioProject PRJNA1135185 and SRA study SRP519594. Searching any of these in the dataset finder brings you back here.

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