title: Ferrous Iron Up-regulation in Fibroblasts of Patients with Beta Propeller Protein-Associated Neurodegeneration (BPAN).
abstract: Mutations inWDR45gene, coding for a beta-propeller protein, have been found in patients affected by Neurodegeneration with Brain Iron Accumulation, NBIA5 (also known as BPAN). BPAN is a movement disorder with Non Transferrin Bound Iron (NTBI) accumulation in the basal ganglia as common hallmark between NBIA classes (Hayflick et al., 2013). WDR45 has been predicted to have a role in autophagy, while the impairment of iron metabolism in the different NBIA subclasses has not currently been clarified. We found the up-regulation of the ferrous iron transporter (-)IRE/Divalent Metal Transporter1 and down-regulation of Transferrin receptor in the fibroblasts of two BPAN affected patients with splicing mutations 235+1G>A (BPAN1) and 517_519ΔVal 173 (BPAN2). The BPAN patients showed a concomitant increase of intracellular ferrous iron after starvation. An altered pattern of iron transporters with iron overload is highlighted in BPAN human fibroblasts, supporting for a role of DMT1 in NBIA. We here present a novel element, about iron accumulation, to the existing knowledge in field of NBIA. Attention is focused to a starvation-dependent iron overload, possibly accounting for iron accumulation in the basal ganglia. Further investigation could clarify iron regulation in BPAN.
authors.affiliation: Section of Pharmacology, Department of Molecular and Translational Medicine, University of Brescia Brescia, Italy.
authors.forename: Rosaria
authors.initials: R
authors.lastname: Ingrassia
authors.affiliation: Section of Pharmacology, Department of Molecular and Translational Medicine, University of Brescia Brescia, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Memo
authors.affiliation: Molecular Neurogenetics Unit, Foundation IRCCS Neurological Institute Carlo Besta Milan, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Garavaglia
keywords: Divalent metal transporter 1 (DMT1); NBIA; WDR45; beta-propeller associated neurodegeneration (BPAN); iron; neurodegeneration