ArticleJournal of neurochemistry2022
A neurodegeneration gene, WDR45, links impaired ferritinophagy to iron accumulation.
Article in Journal of neurochemistry, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 33 citations in OpenAlex.
- Revisiting Inherited Metabolic Diseases (IMDs) Through the Lens of Selective Autophagy.Journal of inherited metabolic disease · 2026Review
- Functional Homology of WIPI4 and Atg18 EnablesInternational journal of molecular sciences · 2026Article
- Therapeutic Advances in Major NBIA Disorders: Current Strategies and Translational Challenges.Neurology international · 2026Review
- Ferritin in ferroptosis: Implications for neurodegenerative diseases (Review).International journal of molecular medicine · 2026Review
- Elevated iron levels in tears of patients diagnosed with WDR45 X-linked optic atrophy.Orphanet journal of rare diseases · 2026Article
- Acidosis, Iron Dyshomeostasis and Inflammatory Injury.International journal of molecular sciences · 2026Review
- Autophagy-Lysosome Pathway Dysfunction in Neurodegeneration and Cancer: Mechanisms and Therapeutic Opportunities.International journal of molecular sciences · 2025Review
- 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
- Biotin Induces Inactive Chromosome X Reactivation and Corrects Physiopathological Alterations in Beta-Propeller-Protein-Associated Neurodegeneration.International journal of molecular sciences · 2025Article
- Ferritin Hinders Ferroptosis in Non-Tumorous Diseases: Regulatory Mechanisms and Potential Consequences.Current protein & peptide science · 2025Review
- Neuronal SLC39A8 deficiency impairs cerebellar development by altering manganese homeostasis.JCI insight · 2024Article
- A c.726C>G (p.Tyr242Ter) nonsense mutation-associated with splicing alteration (NASA) ofHeliyon · 2024Article
- Iron chelators: as therapeutic agents in diseases.Annals of medicine and surgery (2012) · 2024Review
- Loss of WIPI4 in neurodegeneration causes autophagy-independent ferroptosis.Nature cell biology · 2024Article
- Lipid droplet accumulation in Wdr45-deficient cells caused by impairment of chaperone-mediated autophagic degradation of Fasn.Lipids in health and disease · 2024Article
- A burning question from the first international BPAN symposium: is restoration of autophagy a promising therapeutic strategy for BPAN?Autophagy · 2023Article
- Evaluating Manganese, Zinc, and Copper Metal Toxicity on SH-SY5Y Cells in Establishing an Idiopathic Parkinson's Disease Model.International journal of molecular sciences · 2023Article
- Novel mutations and molecular pathways identified in patients with brain iron accumulation disorders.Neurogenetics · 2023Article
- Antioxidants Prevent Iron Accumulation and Lipid Peroxidation, but Do Not Correct Autophagy Dysfunction or Mitochondrial Bioenergetics in Cellular Models of BPAN.International journal of molecular sciences · 2023Article
- Autophagy in Parkinson's Disease.Biomolecules · 2023Review
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Neurodegeneration with brain iron accumulation (NBIA) is a clinically and genetically heterogeneous group of neurodegenerative diseases characterized by the abnormal accumulation of brain iron and the progressive degeneration of the nervous system. One of the recently identified subtypes of NBIA is β-propeller protein-associated neurodegeneration (BPAN). BPAN is caused by de novo mutations in the WDR45/WIPI4 (WD repeat domain 45) gene. WDR45 is one of the four mammalian homologs of yeast Atg18, a regulator of autophagy. WDR45 deficiency in BPAN patients and animal models may result in defects in autophagic flux. However, how WDR45 deficiency leads to brain iron overload remains unclear. To elucidate the role of WDR45, we generated a WDR45-knockout (KO) SH-SY5Y neuroblastoma cell line using CRISPR-Cas9-mediated genome editing. Using these cells, we demonstrated that the non-TF (transferrin)-bound iron pathway dominantly mediated the accumulation of iron. Moreover, the loss of WDR45 led to defects in ferritinophagy, a form of autophagy that degrades the iron storage protein ferritin. We showed that impaired ferritinophagy contributes to iron accumulation in WDR45-KO cells. Iron accumulation was also detected in the mitochondria, which was accompanied by impaired mitochondrial respiration, elevated reactive oxygen species, and increased cell death. Thus, our study links WDR45 to specific iron acquisition pathways and ferritinophagy. Cover Image for this issue: https://doi.org/10.1111/jnc.15388.
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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.