Ferroptosis and Cuproptosis: Mechanism and Crosstalk in Cancer, Neurodegeneration, and Metabolic Syndrome

A special issue of Biomolecules (ISSN 2218-273X). This special issue belongs to the section "Molecular Medicine".

Deadline for manuscript submissions: 30 September 2026 | Viewed by 2265

Special Issue Editor

Special Issue Information

Dear Colleagues,

This special issue explores the emerging concepts of ferroptosis and cuproptosis, two distinct forms of regulated cell death, and their roles in cancer, neurodegeneration, and metabolic syndrome. The scope of the special issue spans the mechanisms underlying ferroptosis and cuproptosis, their interconnection, and their crosstalk in various diseases. Topics covered include but are not limited to, Alzheimer's disease, psychiatric disorders, and colorectal cancer, highlighting how these forms of cell death contribute to disease progression and potential therapeutic strategies. By examining the interplay of iron and copper metabolism in disease pathogenesis, this special issue provides a comprehensive view of how ferroptosis and cuproptosis impact cellular function and contribute to various pathological conditions, opening new avenues for targeted treatment.

Suitable topics include, but are not limited to: Alzheimer's disease, psychiatric disorders, and colorectal cancer.

You may choose our Joint Special Issue in International Journal of Molecular Sciences.

Dr. Rosanna Squitti
Guest Editor

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Keywords

  • ferroptosis
  • cuproptosis
  • Alzheimer's disease
  • colorectal cancer
  • neurodegeneration
  • metabolic syndrome
  • regulated cell death
  • iron metabolism
  • copper metabolism
  • psychiatric disorders

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Published Papers (1 paper)

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Review

28 pages, 3102 KB  
Review
Ferroptosis and Cuproptosis in Cancer and Neurodegeneration: A Comprehensive Review of Modulation by Iron and Copper Chelators and Related Agents
by Iogann Tolbatov and Alessandro Marrone
Biomolecules 2026, 16(3), 348; https://doi.org/10.3390/biom16030348 - 26 Feb 2026
Cited by 2 | Viewed by 1811
Abstract
Dysregulation of iron and copper homeostasis is a pivotal driver of regulated cell death through two distinct yet interconnected modalities: ferroptosis and cuproptosis. This comprehensive review evaluates the therapeutic modulation of these metal-driven pathways within a dual paradigm: their deployment as a cytotoxic [...] Read more.
Dysregulation of iron and copper homeostasis is a pivotal driver of regulated cell death through two distinct yet interconnected modalities: ferroptosis and cuproptosis. This comprehensive review evaluates the therapeutic modulation of these metal-driven pathways within a dual paradigm: their deployment as a cytotoxic weapon in oncology and their inhibition for neuroprotection. We synthesize evidence ranging from small-molecule synergy to advanced nanomedicine, examining how the interplay between iron and copper governs cellular fate in resistant malignancies and neurodegenerative diseases such as Parkinson’s disease and Multiple Sclerosis. In oncology, bimetallic nanoplatforms and CRISPR-Cas9 nano-ionophores exploit “iron addiction” and metabolic vulnerabilities to induce fatal lipid peroxidation and FDX1-mediated proteotoxic stress, often by circumventing efflux transporters like ATP7A/B. Conversely, neuroprotective strategies focus on site-specific chelation, utilizing brain-penetrant molecules like SK4 (targeting the LAT1 transporter) and radical trapping antioxidants like CuII(atsm). Importantly, we elucidate the “iron trap” mechanism, where copper deficiency inactivates multicopper ferroxidases—including ceruloplasmin and hephaestin—thereby triggering iron-dependent ferroptosis. Our analysis reveals a self-amplifying cycle of oxidative damage driven by metal-induced ATP depletion and glutathione exhaustion. By delineating the molecular machinery of iron and copper metabolism, this article provides a roadmap for leveraging regulated cell death to overcome apoptosis resistance in cancer and preserve neural integrity in chronic degeneration. Full article
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