References of "Boussaad, Ibrahim 50001019"
     in
Bookmark and Share    
Full Text
Peer Reviewed
See detailPINK1 deficiency impairs adult neurogenesis of dopaminergic neurons
Brown, Sarah J; Boussaad, Ibrahim UL; Jarazo, Javier UL et al

in Scientific Reports (2021)

Detailed reference viewed: 16 (0 UL)
Full Text
Peer Reviewed
See detailBidirectional Relation Between Parkinson’s Disease and Glioblastoma Multiforme
Mencke, Pauline UL; Hanss, Zoé; Boussaad, Ibrahim UL et al

in Frontiers in Neurology (2020)

Detailed reference viewed: 24 (0 UL)
Full Text
Peer Reviewed
See detailA patient-based model of RNA mis-splicing uncovers treatment targets in Parkinson's disease.
Boussaad, Ibrahim UL; Obermaier, Carolin D.; Hanss, Zoé et al

in Science translational medicine (2020), 12(560),

Parkinson's disease (PD) is a heterogeneous neurodegenerative disorder with monogenic forms representing prototypes of the underlying molecular pathology and reproducing to variable degrees the sporadic ... [more ▼]

Parkinson's disease (PD) is a heterogeneous neurodegenerative disorder with monogenic forms representing prototypes of the underlying molecular pathology and reproducing to variable degrees the sporadic forms of the disease. Using a patient-based in vitro model of PARK7-linked PD, we identified a U1-dependent splicing defect causing a drastic reduction in DJ-1 protein and, consequently, mitochondrial dysfunction. Targeting defective exon skipping with genetically engineered U1-snRNA recovered DJ-1 protein expression in neuronal precursor cells and differentiated neurons. After prioritization of candidate drugs, we identified and validated a combinatorial treatment with the small-molecule compounds rectifier of aberrant splicing (RECTAS) and phenylbutyric acid, which restored DJ-1 protein and mitochondrial dysfunction in patient-derived fibroblasts as well as dopaminergic neuronal cell loss in mutant midbrain organoids. Our analysis of a large number of exomes revealed that U1 splice-site mutations were enriched in sporadic PD patients. Therefore, our study suggests an alternative strategy to restore cellular abnormalities in in vitro models of PD and provides a proof of concept for neuroprotection based on precision medicine strategies in PD. [less ▲]

Detailed reference viewed: 129 (8 UL)