Nature Immunology, Published online: 26 June 2025; doi:10.1038/s41590-025-02194-8

We show that mutations in the CSF1R gene, which cause the rare neurodegenerative disease ALSP, lead to the loss and abnormal activation of microglia. This triggers glial stress and the emergence of disease-associated oligodendrocytes with impaired myelinating potential. These findings suggest potential therapeutic strategies by modulating glial stress pathways or enhancing compensatory microglial support mechanisms.



Summary

A study in Nature Immunology identifies a critical link between CSF1R gene mutations, the cause of the neurodegenerative disease ALSP, and glial dysfunction. The research reveals that these mutations result in the loss and aberrant activation of microglia, inducing stress within other glial cells. Specifically, disease-associated oligodendrocytes with diminished myelinating ability emerge. The findings propose that targeting glial stress pathways or bolstering microglial support mechanisms could offer novel therapeutic avenues for ALSP.

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