Pantothenate rescues iron accumulation in Pantothenate Kinase-
associated neurodegeneration depending on the type of mutation
Mónica Álvarez-Córdoba, Aida Fernández Khoury, Marina Villanueva-Paz,Carmen
Gómez-Navarro, Irene Villalón-García, Juan M. Suárez-Rivero, Suleva Povea-Cabello,
Mario de la Mata, David Cotán, Marta Talaverón-Rey, Antonio J. Pérez-Pulido, Joaquín
J. Salas, Eva Mª Pérez-Villegas, Antonio Díaz-Quintana, José A. Armengol and José A.
Molecular Neurobiology, 2018 in press
- Mutant PANK2 fibroblasts derived from patients show accumulation of iron and
lipofuscin (age pigment). Furthermore, mutant fibroblasts show a characteristic
- Paradoxically, impaired mitochondrial iron metabolism in patient cells induces
cytosolic iron deficiency and a vicious cycle with increased iron uptake which is
accumulated in lipofuscin granules.
- Pantothenate can correct pathological alterations depending on the type of
mutation in mutant fibroblasts.
- Expression levels of mutant PANK2 can be restored by pantothenate in particular
- For the first time, iron accumulation is demonstrated in induced neuronsobtained by
direct reprograming of mutant fibroblasts.
- The positive effect of pantothenate is also confirmed in induced neurons.
- Residual enzyme expression raises the possibility of treatment with pantothenate in
- The methodological strategy described in this manuscript can be also applied to
other NBIA subtypes such as PLAN, BPAN or MPAN.
Electron microscopy image of a PANK2 mutant fibroblast with lipofuscin granules