ArticleCell death & disease2021
Intranasal administration of α-synuclein preformed fibrils triggers microglial iron deposition in the substantia nigra of Macaca fascicularis.
Article in Cell death & disease, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers, 1 of them a synthesis that pooled it.
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Who cites it
41 citing papers in PubMed, 1 synthesis or guideline pooled it, 69 citations in OpenAlex.
- Research trends of ferroptosis and pyroptosis in Parkinson's disease: a bibliometric analysis.Frontiers in molecular neuroscience · 2024Pooled it
- Taurochenodeoxycholic acid alleviates MPPIBRO neuroscience reports · 2026Article
- Ferroptosis-related stress during aging and its relevance to disease.GeroScience · 2026Review
- Microglial Nrf2 Activation Orchestrates Ferroptosis Inhibition and α-Synuclein Clearance in Parkinson's Disease.International journal of molecular sciences · 2026Article
- OTUD6A drives dopaminergic neuronal degeneration of Parkinson's disease through deubiquitinating ACTG1 in neuronal cells.Acta pharmaceutica Sinica. B · 2026Article
- Ferroptosis in Parkinson's disease: a review of molecular mechanisms and emerging therapeutic strategies.Frontiers in neuroscience · 2026Review
- Iron Overload Mediates the Differential Cell Fate of Astrocytes from Neurons and Its Regulatory Mechanisms in Ischemic Stroke.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Focused ultrasound-enhanced nose-to-brain delivery of a therapeutic antibody in a large-animal model.Theranostics · 2026Article
- Ferroptosis and Alzheimer's disease: unraveling the molecular mechanisms and therapeutic opportunities.Frontiers in cell and developmental biology · 2026Review
- Stress-Induced Dysregulation of Brain Iron Metabolism and Its Links to Neurological Disorders.Biology · 2025Review
- The role of microglia in neurodegenerative diseases: from the perspective of ferroptosis.Acta pharmacologica Sinica · 2025Review
- Hypoxia ameliorates neurodegeneration and movement disorder in a mouse model of Parkinson's disease.Nature neuroscience · 2025Article
- Position paper: leveraging non-human primate (NHP) specificities to accelerate Parkinson's disease and ageing research.NPJ Parkinson's disease · 2025Review
- Parkinson Disease Signaling Pathways, Molecular Mechanisms, and Potential Therapeutic Strategies: A Comprehensive Review.International journal of molecular sciences · 2025Review
- The role of ferroptosis in Alzheimer's disease: Mechanisms and therapeutic potential (Review).Molecular medicine reports · 2025Review
- The interplay of iron, oxidative stress, and α-synuclein in Parkinson's disease progression.Molecular medicine (Cambridge, Mass.) · 2025Review
- Lactoferrin as a Candidate Multifunctional Therapeutic in Synucleinopathies.Brain sciences · 2025Review
- Homeostasis and metabolism of iron and other metal ions in neurodegenerative diseases.Signal transduction and targeted therapy · 2025Review
- Lewy body diseases and the gut.Molecular neurodegeneration · 2025Review
- The interplay between α-synuclein aggregation and necroptosis in Parkinson's disease: a spatiotemporal perspective.Frontiers in neuroscience · 2025Review
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Authors and funding
13 authors at 6 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Iron deposition is present in main lesion areas in the brains of patients with Parkinson's disease (PD) and an abnormal iron content may be associated with dopaminergic neuronal cytotoxicity and degeneration in the substantia nigra of the midbrain. However, the cause of iron deposition and its role in the pathological process of PD are unclear. In the present study, we investigated the effects of the nasal mucosal delivery of synthetic human α-synuclein (α-syn) preformed fibrils (PFFs) on the pathogenesis of PD in Macaca fascicularis. We detected that iron deposition was clearly increased in a time-dependent manner from 1 to 17 months in the substantia nigra and globus pallidus, highly contrasting to other brain regions after treatments with α-syn PFFs. At the cellular level, the iron deposits were specifically localized in microglia but not in dopaminergic neurons, nor in other types of glial cells in the substantia nigra, whereas the expression of transferrin (TF), TF receptor 1 (TFR1), TF receptor 2 (TFR2), and ferroportin (FPn) was increased in dopaminergic neurons. Furthermore, no clear dopaminergic neuron loss was observed in the substantia nigra, but with decreased immunoreactivity of tyrosine hydroxylase (TH) and appearance of axonal swelling in the putamen. The brain region-enriched and cell-type-dependent iron localizations indicate that the intranasal α-syn PFFs treatment-induced iron depositions in microglia in the substantia nigra may appear as an early cellular response that may initiate neuroinflammation in the dopaminergic system before cell death occurs. Our data suggest that the inhibition of iron deposition may be a potential approach for the early prevention and treatment of PD.
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