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Review
. 2025 Jun 5;13(6):e70385.
doi: 10.1002/fsn3.70385. eCollection 2025 Jun.

Emerging Links Between Ferroptosis and Neurodegeneration: Implications for Disease Mechanisms and Nutraceutical Interventions

Anwar Ali  1 , Quratulain Babar  2 , Ayesha Saeed  2 , Domenico Sergi  3 , Nenad Naumovski  4 , Isam A Mohamed Ahmed  5 , Ghalia Shamlan  5 , Halah Abdulrahman Hafiz  6 , Muhammad Faisal Manzoor  7   8 , Joanna Trafialek  1 , Felix Kwashie Madilo  9
Affiliations
Review

Emerging Links Between Ferroptosis and Neurodegeneration: Implications for Disease Mechanisms and Nutraceutical Interventions

Anwar Ali et al. Food Sci Nutr. .

Abstract

A relatively recently identified type of controlled cell death termed 'ferroptosis' is driven by iron and characterized by reactive oxygen species (ROS) buildup and lipid peroxidation. This review explores the complex mechanisms underpinning ferroptosis and its potential effects on the onset and development of neurodegenerative diseases. The impact of lipid peroxides, glutathione/glutathione peroxidase 4 (GSH/GPX4), and iron metabolism-targeting small molecule inhibitors and the involvement of nucleic acids, proteins, and phytochemicals as inhibitors of ferroptosis will be discussed. Additionally, we explore the potential of ferroptosis as a therapeutic target for managing neurodegenerative disorders and address the challenges faced in clinical translation. The emerging research on novel drug delivery approaches and nanomaterial-based strategies for efficient ferroptosis inhibition is also described. In conclusion, this review provides a detailed overview of the complex landscape of ferroptosis, providing insights into its molecular mechanisms, inhibitors, and potential therapeutic applications. Understanding the multifaceted role of ferroptosis in disease pathogenesis will pave the way for developing innovative interventions to harness its therapeutic potential in various neurological conditions.

Keywords: aging; ferroptosis; inhibitors; neurodegenerative disorders; nutraceuticals; phytochemicals.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

FIGURE 1
FIGURE 1
Aging leads to altered cellular functioning, followed by oxidative stress, which causes age‐related disorders.
FIGURE 2
FIGURE 2
Cellular signaling of ferroptosis followed by lipid peroxidation, apoptosis, and altered cellular oxidative stress.
FIGURE 3
FIGURE 3
Inhibition of ferroptosis by plant‐based phytochemicals.
FIGURE 4
FIGURE 4
Multiple types of inhibitors are involved in blocking the ferroptosis pathway.
FIGURE 5
FIGURE 5
The interplay of ferroptosis in Alzheimer's disease (AD), Parkinson's disease (PD), and Huntington's disease (HD).
See this image and copyright information in PMC

References

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