PKAN hiPS-Derived Astrocytes Show Impairment of Endosomal Trafficking: A Potential Mechanism Underlying Iron Accumulation.

ABSTRACT: PKAN disease is caused by mutations in the PANK2 gene, encoding the mitochondrial enzyme pantothenate kinase 2, catalyzing the first and key reaction in Coenzyme A (CoA) biosynthetic process. This disorder is characterized by progressive neurodegeneration and excessive iron deposition in the brain. The pathogenic mechanisms of PKAN are still unclear, and the available therapies are only symptomatic. Although iron accumulation is a hallmark of PKAN, its relationship with CoA dysfunction is not clear. We have previously developed hiPS-derived astrocytes from PKAN patients showing iron overload, thus recapitulating the human phenotype. In this work, we demonstrated that PKAN astrocytes presented an increase in transferrin uptake, a key route for cellular iron intake via transfer

SUBMITTER: Ripamonti M 

PROVIDER: S-EPMC9243464 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature