ArticleNeurobiology of disease2015
Mitochondrial iron and energetic dysfunction distinguish fibroblasts and induced neurons from pantothenate kinase-associated neurodegeneration patients.
Article in Neurobiology of disease, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 80 citations in OpenAlex.
- Investigating the Neuroprotective Effects of Saw Palmetto Fruit Extract Against D-Galactose and Aluminum Chloride Induced Alzheimer's Disease: In Vivo Study.Neurochemical research · 2026Article
- Exploring the causal impact of mitochondrial dysfunction on epilepsy: a mendelian randomization study.Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas · 2026Article
- 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
- A therapeutic approach to pantothenate kinase associated neurodegeneration: a pilot study.Orphanet journal of rare diseases · 2024Article
- Endo-Lysosomal Network Disorder Reprograms Energy Metabolism in SorL1-Null Rat Hippocampus.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Mitochondrial iron deficiency triggers cytosolic iron overload in PKAN hiPS-derived astrocytes.Cell death & disease · 2024Article
- 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
- Inherited Disorders of Coenzyme A Biosynthesis: Models, Mechanisms, and Treatments.International journal of molecular sciences · 2023Review
- Development of PPARγ Agonists for the Treatment of Neuroinflammatory and Neurodegenerative Diseases: Leriglitazone as a Promising Candidate.International journal of molecular sciences · 2023Review
- Mitochondrial Iron Metabolism: The Crucial Actors in Diseases.Molecules (Basel, Switzerland) · 2022Review
- Bi-Allelic Mutations in ZebrafishInternational journal of molecular sciences · 2022Article
- Therapeutic approach with commercial supplements for pantothenate kinase-associated neurodegeneration with residual PANK2 expression levels.Orphanet journal of rare diseases · 2022Article
- Hypoxia aggravates ferroptosis in RPE cells by promoting the Fenton reaction.Cell death & disease · 2022Article
- Massive iron accumulation in PKAN-derived neurons and astrocytes: light on the human pathological phenotype.Cell death & disease · 2022Article
- PKAN hiPS-Derived Astrocytes Show Impairment of Endosomal Trafficking: A Potential Mechanism Underlying Iron Accumulation.Frontiers in cellular neuroscience · 2022Article
- NovelFrontiers in aging neuroscience · 2022Article
- Metabolism of cancer cells commonly responds to irradiation by a transient early mitochondrial shutdown.iScience · 2021Article
- Coenzyme a Biochemistry: From Neurodevelopment to Neurodegeneration.Brain sciences · 2021Review
- Down regulation of the expression of mitochondrial phosphopantetheinyl-proteins in pantothenate kinase-associated neurodegeneration: pathophysiological consequences and therapeutic perspectives.Orphanet journal of rare diseases · 2021Article
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Pantothenate kinase-associated neurodegeneration is an early onset autosomal recessive movement disorder caused by mutation of the pantothenate kinase-2 gene, which encodes a mitochondrial enzyme involved in coenzyme A synthesis. The disorder is characterised by high iron levels in the brain, although the pathological mechanism leading to this accumulation is unknown. To address this question, we tested primary skin fibroblasts from three patients and three healthy subjects, as well as neurons induced by direct fibroblast reprogramming, for oxidative status, mitochondrial functionality and iron parameters. The patients' fibroblasts showed altered oxidative status, reduced antioxidant defence, and impaired cytosolic and mitochondrial aconitase activities compared to control cells. Mitochondrial iron homeostasis and functionality analysis of patient fibroblasts indicated increased labile iron pool content and reactive oxygen species development, altered mitochondrial shape, decreased membrane potential and reduced ATP levels. Furthermore, analysis of induced neurons, performed at a single cell level, confirmed some of the results obtained in fibroblasts, indicating an altered oxidative status and signs of mitochondrial dysfunction, possibly due to iron mishandling. Thus, for the first time, altered biological processes have been identified in vitro in live diseased neurons. Moreover, the obtained induced neurons can be considered a suitable human neuronal model for the identification of candidate therapeutic compounds for this disease.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.