REVIEW article
Front. Neurosci.
Sec. Neurodegeneration
Ferroptosis in Parkinson's Disease: A Review of Molecular Mechanisms and Emerging Therapeutic Strategies
Provisionally accepted
- 1Department of Neurology, Yantaishan Hospital, Yantai, China
- 2Shandong Provincial Chronic Disease Hospital, Qingdao, China
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Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by the loss of dopaminergic(DA) neurons in the substantia nigra and the presence of Lewy bodies containing aggregated α-Synα-synuclein (α-Synα-syn). While these pathological hallmarks are well-established, the mechanisms underlying neuronal death remain incompletely understood. Emerging evidence highlights ferroptosis, an iron-dependent form of regulated cell death driven by lipid peroxidation, as a critical pathway in PD pathogenesis. This review synthesizes recent advances elucidating the synergistic interplay between α-Synα-syn aggregation and ferroptosis. We detail how α-Synα-syn aggregation not only directly induces ferroptosis but also disrupts iron homeostasis, while iron accumulation in turn accelerates α-Synα-syn fibrillation and oxidative stress, forming a vicious cycle that propagates neurodegeneration. Furthermore, we explore the amplifying role of glial cells—microglia and astrocytes—in this process through the promotion of neuroinflammation, oxidative damage, and dysregulation of iron metabolism. Finally, we discuss promising therapeutic strategies targeting this α-Synα-syn-ferroptosis axis, including α-Synα-syn aggregation inhibitors, iron chelators, and glia-modulating agents, highlighting their potential as disease-modifying interventions. Together, these insights underscore ferroptosis as a central mechanism in PD and offer new avenues for developing targeted therapies.
Keywords: ferroptosis, iron metabolism, neurodegeneration, Parkinson's disease (PD), therapeutic targets
Received: 04 Jan 2026; Accepted: 09 Feb 2026.
Copyright: © 2026 Wang, Zhang and Guo. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Lingling Wang
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