TY - JOUR
T1 - Ferrous iron up-regulation in fibroblasts of patients with beta propeller protein-associated neurodegeneration (BPAN)
AU - Ingrassia, Rosaria
AU - Memo, Maurizio
AU - Garavaglia, Barbara
PY - 2017/2/17
Y1 - 2017/2/17
N2 - Mutations in WDR45 gene, 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.
AB - Mutations in WDR45 gene, 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.
KW - Beta-propeller associated neurodegeneration (BPAN)
KW - Divalent metal transporter 1 (DMT1)
KW - Iron
KW - NBIA
KW - Neurodegeneration
KW - WDR45
UR - http://www.scopus.com/inward/record.url?scp=85014712930&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85014712930&partnerID=8YFLogxK
U2 - 10.3389/fgene.2017.00018
DO - 10.3389/fgene.2017.00018
M3 - Article
AN - SCOPUS:85014712930
VL - 8
JO - Frontiers in Genetics
JF - Frontiers in Genetics
SN - 1664-8021
IS - FEB
M1 - 18
ER -