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Updated: Dec 12, 2025

Assessing Iron Deposition in the Brains of 5xFAD Mice by Perls'/DAB Staining
Published on: May 23, 2025
Impaired proteasome activity and neurodegeneration with brain iron accumulation in FBXO7 defect
Marta Correa-Vela1,2, Vincenzo Lupo3,4, Marta Montpeyó5
1Department of Pediatric Neurology, Hospital Universitari Vall d'Hebron, Vall d´Hebron Institut de Recerca, Barcelona, Spain.
Abstract:
FBXO7 is implicated in the ubiquitin-proteasome system and parkin-mediated mitophagy. FBXO7defects cause a levodopa-responsive parkinsonian-pyramidal syndrome(PPS).
Methods:
We investigated the disease molecular bases in a child with PPS and brain iron accumulation.
Results:
A novel homozygous c.368C>G (p.S123*) FBXO7 mutation was identified in a child with spastic paraplegia, epilepsy, cerebellar degeneration, levodopa nonresponsive parkinsonism, and brain iron deposition. Patient's fibroblasts assays demonstrated an absence of FBXO7 RNA expression leading to impaired proteasome degradation and accumulation of poly-ubiquitinated proteins.
Conclusion:
This novel FBXO7 phenotype associated with impaired proteasome activity overlaps with neurodegeneration with brain iron accumulation disorders.
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