ArticlePloS one2017
iPSC-derived neuronal models of PANK2-associated neurodegeneration reveal mitochondrial dysfunction contributing to early disease.
Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 49 citations in OpenAlex.
- Iron Dysregulation in Neurodegeneration with Brain Iron Accumulation (NBIA): Links between Mutations Occurring in BPAN, PKAN, MPAN and PLAN Types and Iron Metabolism.Molecular neurobiology · 2025Review
- Beyond the optic disc: Investigating gender-based differences in optic neuritis.World journal of clinical cases · 2025Review
- Article
- Impaired mitochondrial integrity and compromised energy production underscore the mechanism underlying CoASY protein-associated neurodegeneration.Cellular and molecular life sciences : CMLS · 2025Article
- Iron Dyshomeostasis in Neurodegeneration with Brain Iron Accumulation (NBIA): Is It the Cause or the Effect?Cells · 2024Review
- Iron imbalance in neurodegeneration.Molecular psychiatry · 2024Review
- Patient-Derived Cellular Models for Polytarget Precision Medicine in Pantothenate Kinase-Associated Neurodegeneration.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Alpha-lipoic acid supplementation corrects pathological alterations in cellular models of pantothenate kinase-associated neurodegeneration with residual PANK2 expression levels.Orphanet journal of rare diseases · 2023Article
- PPAR Gamma Agonist Leriglitazone Recovers Alterations Due to Pank2-Deficiency in hiPS-Derived Astrocytes.Pharmaceutics · 2023Article
- Evidence for a Conserved Function of Eukaryotic Pantothenate Kinases in the Regulation of Mitochondrial Homeostasis and Oxidative Stress.International journal of molecular sciences · 2022Article
- PKAN pathogenesis and treatment.Molecular genetics and metabolism · 2022Review
- Bi-Allelic Mutations in ZebrafishInternational journal of molecular sciences · 2022Article
- Cerebral Iron Deposition in Neurodegeneration.Biomolecules · 2022Review
- Massive iron accumulation in PKAN-derived neurons and astrocytes: light on the human pathological phenotype.Cell death & disease · 2022Article
- Neurodegenerative Disorders: Spotlight on Sphingolipids.International journal of molecular sciences · 2021Review
- [Research advances in the pathogenesis and treatment of neurodegeneration with brain iron accumulation].Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics · 2021Article
- Exploring Yeast as a Study Model of Pantothenate Kinase-Associated Neurodegeneration and for the Identification of Therapeutic Compounds.International journal of molecular sciences · 2020Article
- Neuronal Ablation of CoA Synthase Causes Motor Deficits, Iron Dyshomeostasis, and Mitochondrial Dysfunctions in a CoPAN Mouse Model.International journal of molecular sciences · 2020Article
- Mitochondrial Dysfunction, Oxidative Stress and Neuroinflammation in Neurodegeneration with Brain Iron Accumulation (NBIA).Antioxidants (Basel, Switzerland) · 2020Review
- A pantothenate kinase-deficient mouse model reveals a gene expression program associated with brain coenzyme a reduction.Biochimica et biophysica acta. Molecular basis of disease · 2020Article
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
Abstract
Mutations in PANK2 lead to neurodegeneration with brain iron accumulation. PANK2 has a role in the biosynthesis of coenzyme A (CoA) from dietary vitamin B5, but the neuropathological mechanism and reasons for iron accumulation remain unknown. In this study, atypical patient-derived fibroblasts were reprogrammed into induced pluripotent stem cells (iPSCs) and subsequently differentiated into cortical neuronal cells for studying disease mechanisms in human neurons. We observed no changes in PANK2 expression between control and patient cells, but a reduction in protein levels was apparent in patient cells. CoA homeostasis and cellular iron handling were normal, mitochondrial function was affected; displaying activated NADH-related and inhibited FADH-related respiration, resulting in increased mitochondrial membrane potential. This led to increased reactive oxygen species generation and lipid peroxidation in patient-derived neurons. These data suggest that mitochondrial deficiency is an early feature of the disease process and can be explained by altered NADH/FADH substrate supply to oxidative phosphorylation. Intriguingly, iron chelation appeared to exacerbate the mitochondrial phenotype in both control and patient neuronal cells. This raises caution for the use iron chelation therapy in general when iron accumulation is absent.
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