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

ABSTRACT: 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE272138 | GEO | 2025/11/13

REPOSITORIES: GEO

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

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

| PRJNA1135185 | ENA

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