Neurodegeneration with brain iron accumulation: Insights into the mitochondria dysregulation.

NBIA (Neurodegeneration with brain iron accumulation) is a group of inherited neurologic disorders characterized by marked genetic heterogeneity, in which iron atypical accumulates in basal ganglia resulting in brain magnetic resonance imaging changes, histopathological abnormalities, and neuropsychiatric clinical symptoms. With the rapid development of high-throughput sequencing technologies, ten candidate genes have been identified, including PANK2, PLA2G6, C19orf12, WDR45, FA2H, ATP13A2, FTL, CP, C2orf37, and COASY. They are involved in seemingly unrelated cellular pathways, such as iron homeostasis (FTL, CP), lipid metabolism (PLA2G6, C19orf12, FA2H), Coenzyme A synthesis (PANK2, COASY), and autophagy (WDR45, ATP13A2). In particular, PANK2, COASY, PLA2G6, and C19orf12 are located on mitochondria, which associate with certain subtypes of NBIA showing mitochondria dysregulation. However, the relationships among those four genes are still unclear. Therefore, this review is specifically focused on dysregulation of mitochondria in NBIA and afore-mentioned four genes, with summaries of both pathological and clinical findings.

• Publication year

  2019

• Venue

  Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie

• Publication date

  2019-10-01

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1016/j.biopha.2019.109068PMID 31404774
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Ferroptosis as a target for protection against cardiomyopathy

  2019cited by this paper
• Targeting ferroptosis: A novel therapeutic strategy for the treatment of mitochondrial disease-related epilepsy

  2019cited by this paper
• Impaired iPLA2β activity affects iron uptake and storage without iron accumulation: An in vitro study excluding decreased iPLA2β activity as the cause of iron deposition in PLAN.

  2019cited by this paper
• Long noncoding RNA LINC00336 inhibits ferroptosis in lung cancer by functioning as a competing endogenous RNA

  2019cited by this paper
• Pantothenate Rescues Iron Accumulation in Pantothenate Kinase-Associated Neurodegeneration Depending on the Type of Mutation

  2018cited by this paper
• Inborn errors of coenzyme A metabolism and neurodegeneration

  2018cited by this paper
• A G3BP1-Interacting lncRNA Promotes Ferroptosis and Apoptosis in Cancer via Nuclear Sequestration of p53.

  2018cited by this paper
• Neurodegeneration with brain iron accumulation.

  2018cited by this paper
• Impaired Transferrin Receptor Palmitoylation and Recycling in Neurodegeneration with Brain Iron Accumulation.

  2018cited by this paper
• Lowered iPLA2&ggr; activity causes increased mitochondrial lipid peroxidation and mitochondrial dysfunction in a rotenone‐induced model of Parkinson's disease

  2018cited by this paper
• Induction of ferroptosis and mitochondrial dysfunction by oxidative stress in PC12 cells

  2018cited by this paper
• EGLN1/c-Myc Induced Lymphoid-Specific Helicase Inhibits Ferroptosis through Lipid Metabolic Gene Expression Changes

  2017cited by this paper
• Changes in Red Blood Cell membrane lipid composition: A new perspective into the pathogenesis of PKAN.

  2017cited by this paper
• Chromatin remodeling factor lymphoid-specific helicase inhibits ferroptosis through lipid metabolic genes in lung cancer progression

  2017cited by this paper
• iPSC-derived neuronal models of PANK2-associated neurodegeneration reveal mitochondrial dysfunction contributing to early disease

  2017cited by this paper
• A Novel Deletion Mutation of Exon 2 of the C19orf12 Gene in an Omani Family with Mitochondrial Membrane Protein-Associated Neurodegeneration (MPAN).

  2017cited by this paper
• Novel mutations in PANK2 and PLA2G6 genes in patients with neurodegenerative disorders: two case reports

  2017cited by this paper
• A de novo C19orf12 heterozygous mutation in a patient with MPAN.

  2017cited by this paper
• The p.Thr11Met mutation in c19orf12 is frequent among adult Turkish patients with MPAN.

  2017cited by this paper
• Live or let die: Neuroprotective and anti-cancer effects of nutraceutical antioxidants.

  2017cited by this paper
• Neuroprotective effect of deferoxamine on N-methyl-D-aspartate-induced excitotoxicity in RGC-5 cells

  2017cited by this paper
• Heart failure–induced activation of phospholipase iPLA2γ generates hydroxyeicosatetraenoic acids opening the mitochondrial permeability transition pore

  2017cited by this paper
• Clinical and genetic features of PKAN patients in a tertiary centre in Turkey.

  2017cited by this paper
• Coenzyme A corrects pathological defects in human neurons of PANK2‐associated neurodegeneration

  2016cited by this paper
• Neurodegeneration with brain iron accumulation: A case report

  2016cited by this paper
• Identification of ACSL4 as a biomarker and contributor of ferroptosis.

  2016cited by this paper
• Down-regulation of coasy, the gene associated with NBIA-VI, reduces Bmp signaling, perturbs dorso-ventral patterning and alters neuronal development in zebrafish

  2016cited by this paper
• Ferroptosis: process and function

  2016cited by this paper
• Knock-down of pantothenate kinase 2 severely affects the development of the nervous and vascular system in zebrafish, providing new insights into PKAN disease

  2016cited by this paper
• Mutations of C19orf12, coding for a transmembrane glycine zipper containing mitochondrial protein, cause mis-localization of the protein, inability to respond to oxidative stress and increased mitochondrial Ca2+

  2015cited by this paper
• Review: Insights into molecular mechanisms of disease in neurodegeneration with brain iron accumulation: unifying theories

  2015cited by this paper
• The novel mitochondrial iron chelator 5-((methylamino)methyl)-8-hydroxyquinoline protects against mitochondrial-induced oxidative damage and neuronal death.

  2015cited by this paper
• Mitochondrial iron and energetic dysfunction distinguish fibroblasts and induced neurons from pantothenate kinase-associated neurodegeneration patients

  2015cited by this paper
• Modeling human Coenzyme A synthase mutation in yeast reveals altered mitochondrial function, lipid content and iron metabolism

  2015cited by this paper
• Neuroaxonal dystrophy in PLA2G6 knockout mice

  2015cited by this paper
• C19orf12 gene mutations in patients with neurodegeneration with brain iron accumulation.

  2015cited by this paper
• Acanthocytosis and the c.680 A>G Mutation in the PANK2 Gene: A Study Enrolling a Cohort of PKAN Patients from the Dominican Republic

  2015cited by this paper
• Regulation of ferroptotic cancer cell death by GPX4.

  2014cited by this paper
• Mitochondrial iron-sulfur protein biogenesis and human disease.

  2014cited by this paper
• Novel homozygous PANK2 mutation causing atypical pantothenate kinase-associated neurodegeneration (PKAN) in a Cypriot family.

  2014cited by this paper
• Exome sequence reveals mutations in CoA synthase as a cause of neurodegeneration with brain iron accumulation.

  2014cited by this paper
• PLA2G6-associated neurodegeneration (PLAN): Further expansion of the clinical, radiological and mutation spectrum associated with infantile and atypical childhood-onset disease

  2014cited by this paper
• Regulation of cellular iron metabolism and its implications in lung cancer progression

  2014cited by this paper
• New NBIA subtype

  2013cited by this paper
• Pantethine treatment is effective in recovering the disease phenotype induced by ketogenic diet in a pantothenate kinase-associated neurodegeneration mouse model

  2013cited by this paper
• PANK2 and C19orf12 mutations are common causes of neurodegeneration with brain iron accumulation

  2013cited by this paper
• Proteomic Mapping of Mitochondria in Living Cells via Spatially Restricted Enzymatic Tagging

  2013cited by this paper
• Cofilin/Twinstar Phosphorylation Levels Increase in Response to Impaired Coenzyme A Metabolism

  2012cited by this paper
• Metabolic consequences of mitochondrial coenzyme A deficiency in patients with PANK2 mutations.

  2012cited by this paper
• Pantothenate kinase-associated neurodegeneration: altered mitochondria membrane potential and defective respiration in Pank2 knock-out mouse model

  2012cited by this paper
• Ferroptosis: an iron-dependent form of nonapoptotic cell death.

  2012cited by this paper
• Pantothenate kinase-associated neurodegeneration is not a synucleinopathy

  2012cited by this paper
• Neuroimaging Features of Neurodegeneration with Brain Iron Accumulation

  2012cited by this paper
• Germline Deletion of Pantothenate Kinases 1 and 2 Reveals the Key Roles for CoA in Postnatal Metabolism

  2012cited by this paper
• Iron‐related MRI images in patients with pantothenate kinase–associated neurodegeneration (PKAN) treated with deferiprone: Results of a phase II pilot trial

  2011cited by this paper
• Neuroaxonal Dystrophy in Calcium-Independent Phospholipase A2β Deficiency Results from Insufficient Remodeling and Degeneration of Mitochondrial and Presynaptic Membranes

  2011cited by this paper
• Impaired Coenzyme A metabolism affects histone and tubulin acetylation in Drosophila and human cell models of pantothenate kinase associated neurodegeneration

  2011cited by this paper
• Absence of an orphan mitochondrial protein, c19orf12, causes a distinct clinical subtype of neurodegeneration with brain iron accumulation.

  2011cited by this paper
• Young-Onset Parkinsonism in a Hong Kong Chinese Man With Adult-Onset Hallervorden–Spatz Syndrome

  2011cited by this paper
• Genetic Ablation of PLA2G6 in Mice Leads to Cerebellar Atrophy Characterized by Purkinje Cell Loss and Glial Cell Activation

  2011cited by this paper
• Novel histopathologic findings in molecularly-confirmed pantothenate kinase-associated neurodegeneration.

  2011cited by this paper
• A pilot trial of deferiprone for neurodegeneration with brain iron accumulation

  2011cited by this paper
• Phospholipase A2 enzymes: physical structure, biological function, disease implication, chemical inhibition, and therapeutic intervention.

  2011cited by this paper
• Diffusion tensor magnetic resonance imaging tractography in progressive supranuclear palsy

  2011cited by this paper
• Real-world use of iron chelators.

  2011cited by this paper
• Pantethine rescues a Drosophila model for pantothenate kinase–associated neurodegeneration

  2010cited by this paper
• Indian‐subcontinent NBIA: Unusual phenotypes, novel PANK2 mutations, and undetermined genetic forms

  2010cited by this paper
• Pantothenate kinase-associated neurodegeneration: insights from a Drosophila model.

  2009cited by this paper
• Calcium‐independent phospholipase A2 mediates proliferation of human promonocytic U937 cells

  2008cited by this paper
• De novo CoA biosynthesis is required to maintain DNA integrity during development of the Drosophila nervous system.

  2008cited by this paper
• Neuroaxonal Dystrophy Caused by Group VIA Phospholipase A2 Deficiency in Mice: A Model of Human Neurodegenerative Disease

  2008cited by this paper
• Regression of symptoms after selective iron chelation therapy in a case of neurodegeneration with brain iron accumulation

  2008cited by this paper
• Novel mutation in the PANK2 gene leads to pantothenate kinase-associated neurodegeneration in a Pakistani family.

  2007cited by this paper
• Deprivation of pantothenic acid elicits a movement disorder and azoospermia in a mouse model of pantothenate kinase-associated neurodegeneration

  2007cited by this paper
• PANK2 gene analysis confirms genetic heterogeneity in neurodegeneration with brain iron accumulation (NBIA) but mutations are rare in other types of adult neurodegenerative disease.

  2006cited by this paper
• Identification of a novel CoA synthase isoform, which is primarily expressed in the brain.

  2006cited by this paper
• Genotypic and phenotypic spectrum of PANK2 mutations in patients with neurodegeneration with brain iron accumulation

  2006cited by this paper
• Altered Neuronal Mitochondrial Coenzyme A Synthesis in Neurodegeneration with Brain Iron Accumulation Caused by Abnormal Processing, Stability, and Catalytic Activity of Mutant Pantothenate Kinase 2

  2005cited by this paper
• Novel compound heterozygous mutations in the PANK2 gene in a Chinese patient with atypical pantothenate kinase‐associated neurodegeneration

  2005cited by this paper
• The diverse phenotype and genotype of pantothenate kinase-associated neurodegeneration

  2005cited by this paper
• Subcellular Localization and Regulation of Coenzyme A Synthase*

  2003cited by this paper
• Oxidant-mediated AA release from astrocytes involves cPLA(2) and iPLA(2).

  2003cited by this paper
• Genetic, clinical, and radiographic delineation of Hallervorden-Spatz syndrome.

  2003cited by this paper
• Complete Reconstitution of the Human Coenzyme A Biosynthetic Pathway via Comparative Genomics*

  2002cited by this paper
• Hallervorden‐Spatz disease: Cysteine accumulation and cysteine dioxygenase deficiency in the globus pallidus

  1985cited by this paper
• The regional distribution and cellular localization of iron in the rat brain.

  1984cited by this paper
• THE EFFECT OF AGE ON THE NON‐HAEMIN IRON IN THE HUMAN BRAIN

  1958cited by this paper

• Sensitivity of primary mitochondrial disease fibroblasts to ferroptosis: The role of intracellular iron.

  2026cites this paper
• Tetrahydrocurcumin exhibits neuroprotective effects by inhibiting neuron ferroptosis via activity of iPLA2β/p38 MAPK phosphorylation in rat TBI model

  2025cites this paper
• Impaired mitochondrial integrity and compromised energy production underscore the mechanism underlying CoASY protein-associated neurodegeneration

  2025cites this paper
• Targeting pantothenate kinases in human diseases: Biochemistry and pharmacotherapy.

  2025cites this paper
• Mapping Disorders with Neurological Features Through Mitochondrial Impairment Pathways: Insights from Genetic Evidence

  2025cites this paper
• Elevating the significance of legume intake: A novel strategy to counter aging-related mitochondrial dysfunction and physical decline.

  2024cites this paper
• Understanding the Mechanism of Ferroptosis in Neurodegenerative Diseases.

  2024cites this paper
• Lutein, a versatile carotenoid: Insight on neuroprotective potential and recent advances.

  2024cites this paper
• Metabolic alterations in fibroblasts of patients presenting with the MPAN subtype of neurodegeneration with brain iron accumulation (NBIA).

  2024cites this paper
• Metabolic impairments in neurodegeneration with brain iron accumulation.

  2024cites this paper
• Differential diagnosis of chorea (guidelines of the German Neurological Society)

  2023cites this paper
• Phenotype and genotype heterogeneity of PLA2G6-associated neurodegeneration in a cohort of pediatric and adult patients

  2023cites this paper
• Development of PPARγ Agonists for the Treatment of Neuroinflammatory and Neurodegenerative Diseases: Leriglitazone as a Promising Candidate

  2023cites this paper
• Fatty Acid 2-Hydroxylase and 2-Hydroxylated Sphingolipids: Metabolism and Function in Health and Diseases

  2023influential citation
• The role of mitochondrial dynamics in disease

  2023influential citation
• Exploring the genetic and genomic connection underlying neurodegeneration with brain iron accumulation and the risk for Parkinson’s disease

  2022cites this paper
• C19orf12 ablation causes ferroptosis in mitochondrial membrane protein-associated with neurodegeneration.

  2022cites this paper
• Case Report: Identification of a De novo C19orf12 Variant in a Patient With Mitochondrial Membrane Protein–Associated Neurodegeneration

  2022cites this paper
• ATP13A2 protects dopaminergic neurons in Parkinson's disease: from biology to pathology

  2022cites this paper
• Novel PANK2 Mutations in Patients With Pantothenate Kinase-Associated Neurodegeneration and the Genotype–Phenotype Correlation

  2022cites this paper
• Cerebral Iron Deposition in Neurodegeneration

  2022cites this paper
• A patient with Beta-Propeller Protein-Associated Neurodegeneration: a new missense mutation of the WDR45 gene

  2022cites this paper
• Long-Term Neuroradiological and Clinical Evaluation of NBIA Patients Treated with a Deferiprone Based Iron-Chelation Therapy

  2022cites this paper
• Iron- and Neuromelanin-Weighted Neuroimaging to Study Mitochondrial Dysfunction in Patients with Parkinson’s Disease

  2022cites this paper
• THE CONSEQUENCES OF PUTATIVE INFLAMMATION ON BRAIN TRACE METAL BIOLOGY by

  2022cites this paper
• Dystonia, Chorea, and Ataxia: Three Challenging Cases

  2022cites this paper
• SPG43 and ALS-like syndrome in the same family due to compound heterozygous mutations of the C19orf12 gene: a case description and brief review

  2021cites this paper
• A neurodegeneration gene, WDR45, links impaired ferritinophagy to iron accumulation

  2021cites this paper
• Infantile Developmental Delay Caused by Pathogenic Mutation in WDR45 Gene and Literature Review

  2021cites this paper
• Gossypitrin, A Naturally Occurring Flavonoid, Attenuates Iron-Induced Neuronal and Mitochondrial Damage

  2021cites this paper
• WDR45, one gene associated with multiple neurodevelopmental disorders

  2021cites this paper
• Personalized Perturbation Profiles Reveal Concordance between Autism Blood Transcriptome Datasets

  2021cites this paper
• Targeting Mitochondrial Impairment in Parkinson's Disease: Challenges and Opportunities

  2021cites this paper
• Ratiometric fluorescent probes based on through-bond energy transfer of cyanine donors to near-infrared hemicyanine acceptors for mitochondrial pH detection and monitoring of mitophagy.

  2020cites this paper
• Overdosing on iron: Elevated iron and degenerative brain disorders

  2020cites this paper
• The infantile neuroaxonal dystrophy rating scale (INAD-RS)

  2020cites this paper
• Mitochondrial Dysfunction, Oxidative Stress and Neuroinflammation in Neurodegeneration with Brain Iron Accumulation (NBIA)

  2020cites this paper
• Egr2 upregulation induced mitochondrial iron overload implicating in sevoflurane-induced cognitive deficits in developing mice

  2020cites this paper
• The impact of brain iron accumulation on cognition: A systematic review

  2020cites this paper