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Review
. 2025 Mar;33(3):1271-1287.
doi: 10.1007/s10787-025-01672-7. Epub 2025 Feb 25.

Ferroptosis role in complexity of cell death: unrevealing mechanisms in Parkinson's disease and therapeutic approaches

Anupam Awasthi  1 , Kousik Maparu  1 , Shamsher Singh  2
Affiliations
Review

Ferroptosis role in complexity of cell death: unrevealing mechanisms in Parkinson's disease and therapeutic approaches

Anupam Awasthi et al. Inflammopharmacology. 2025 Mar.

Abstract

Parkinson's disease (PD), a common neurodegenerative disorder, is characterized by progressive loss of dopaminergic neurons, and accumulation of α-synuclein in the substantial nigra. Emerging evidence identifies ferroptosis as a regulated iron-dependent cell death mechanism marked by excessive lipid peroxidation (LPO) as a key contributor to PD pathogenesis. Ferroptosis is intertwined with critical disease processes such as aggregation of α-synuclein protein, oxidative stress generation, mitochondrial alteration, iron homeostasis dysregulation, and neuroinflammation. This mechanism disrupts cellular homeostasis by impairing iron metabolism and antioxidant pathways like the xc-/glutathione/GPX4 axis and the CoQ10 pathway. This review consolidates current advancements in understanding ferroptosis in these mechanisms, increasing interest in contribution to PD pathology. In addition, it explores the latest developments in ferroptosis-targeting pharmacological agents, including their application in the preclinical and clinical study, and highlights their potential to revolutionize PD management. Unraveling the interplay between ferroptosis and PD offers a transformative perspective, paving the way for innovative therapies to combat this debilitating disease condition.

Keywords: Fenton reaction; Ferroptosis; Iron dysregulation; Lipid peroxidation (LPO); Neuroinflammation; Parkinson’s disease (PD); α-Synuclein.

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Conflict of interest statement

Declarations. Ethical approval: Not applicable. Consent to publication: Not applicable. Conflicts of interest: All authors declared the absence of any financial or personal conflicts about this work.

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