Apostolos Papandreou, Nivedita Singh, Lorita Gianfrancesco, Dimitri Budinger, Katy Barwick, Alexander Agrotis, Christin Luft, Ying Shao, An-Sofie Lenaerts, Allison Gregory, Suh Young Jeong, Penelope Hogarth, Susan Hayflick, Serena Barral, Janos Kriston-Vizi, Paul Gissen, Manju A Kurian, Robin Ketteler
Beta-Propeller Protein-Associated Neurodegeneration (BPAN) is one of the commonest forms of Neurodegeneration with Brain Iron Accumulation, caused by mutations in the gene encoding the autophagy-related protein, WDR45. The mechanisms linking autophagy, iron overload and neurodegeneration in BPAN are poorly understood and, as a result, there are currently no disease-modifying treatments for this progressive disorder. We have developed a patient-derived, induced pluripotent stem cell (iPSC)-based midbrain dopaminergic neuronal cell model of BPAN (3 patient, 2 age-matched controls and 2 isogenic control lines) which shows defective autophagy and aberrant gene expression in key neurodegenerative, neurodevelopmental and collagen pathways...
September 13, 2023: bioRxiv