Disruption of CSF-1 receptor-mediated metal ion homeostasis in the murine brain promotes neurodegenerative disease - PubMed
3 hours ago
- #microglial dysfunction
- #metal ion homeostasis
- #neurodegenerative disease
- Dominant-inactivating mutations in CSF-1R cause CSF-1R related leukoencephalopathy (CRL).
- CRL is modeled in Csf1r+/- mice and is caused by microglial dysfunction.
- Single-nucleus RNA sequencing revealed metal ion accumulation in brain macrophages of Csf1r+/- mice.
- Reduction of metallothionein 1 (Mt1) and 3 (Mt3) gene expression was common in glial and neuronal cells.
- Overexpression of Mt1 restored metal ion homeostasis and prevented behavioral deficits.
- Deletion of Mt3 had disease-enhancing effects.
- CSF-1R regulates metal ion homeostasis via metallothioneins in the brain.