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Cited by 12Iron Metabolism and DisordersNeurological diseases and metabolismFerroptosis and cancer prognosis

Ferritin in ferroptosis: implications for neurodegenerative diseases (Review)

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Chen, Wenjing, Tian, Heng, Wei, Ran, Chen, Xiaomei, Jia, Yiwen·2026·International Journal of Molecular Medicine
DOI 10.3892/ijmm.2026.5790PMC PMC12987564
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Abstract

Neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis, are characterized by progressive loss of neurons. Although the precise pathogenesis of such diseases is complex and multifactorial, several molecular pathways have been implicated, including the aggregation of misfolded proteins, mitochondrial dysfunction, oxidative stress, neuroinflammation and disrupted iron homeostasis. Emerging evidence has underscored the pivotal role of ferroptosis, an iron‑dependent, non‑apoptotic form of cell death, in neurodegenerative disease progression. Ferritin, characterized by a 24‑subunit hollow sphere structure composed of heavy and light chains, plays a key role in the network regulating cerebral iron homeostasis. In response to cellular iron overload, ferritin expression is upregulated to sequester labile iron and mitigate Fenton reaction‑mediated toxicity, thus exerting a cytoprotective function. Paradoxically, ferritin can be degraded via ferritinophagy, a selective autophagic process that releases toxic ferrous iron and directly triggers ferroptosis. This review systematically reviews the role of ferritin within the iron homeostasis network to elucidate the connection between the dysregulation of iron metabolism and the pathological mechanisms of neurodegenerative diseases. The study focused on the potential role of ferritin as a biomarker for early diagnosis, therapeutic strategies targeting ferritin pathways to restore iron homeostasis and the clinical translational value of magnetic resonance imaging‑based non‑invasive quantification of cerebral iron deposition. It is crucial to elucidate the multidimensional roles of ferritin in neurodegeneration to provide a theoretical foundation for precision diagnostic and therapeutic approaches.

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Cited by

Sorted by citations

Authors
Chen, W., Tian, H., Wei, R., Chen, X., & Jia, Y.
Affiliations
  • Anhui Medical University (CN)
  • First Affiliated Hospital of Anhui Medical University (CN)
  • Department of Cardiology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, P.R. China
Corresponding author
Jia, Yiwen
ORCID
Venue
International Journal of Molecular Medicine
Publisher
Spandidos Publications
Published
2026-03-12
Volume
57
Issue
5
Pages
1-18
ISSN
  • 1107-3756 (ISSN-L)
  • 1791-244X
DOI
10.3892/ijmm.2026.5790
PMC
PMC12987564
OpenAlex
W7135128082
Cited by
12
References
0
Citations by year
2026: 12
FWCI
15.56
Type
journal article
Language
en
Open access
Licence
cc-by-nc-nd
Locations
  • International Journal of Molecular Medicine (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
  • Life Sciences › Neuroscience › Neurology › Neurological diseases and metabolism
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Ferroptosis and cancer prognosis
Keywords
ferritin, ferroptosis, neurodegenerative diseases, iron homeostasis, ferritinophagy, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, Fenton reaction, labile iron, biomarkers, autophagy
MeSH terms
Ferroptosis, Animals, Ferritins, Homeostasis, Humans, Iron, Neurodegenerative Diseases

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