# Ferroptosis in Parkinson’s disease: a review of molecular mechanisms and emerging therapeutic strategies

## TL;DR

This review explores how ferroptosis, a type of cell death, contributes to Parkinson’s disease and highlights new treatment strategies targeting this process.

## Contribution

The paper introduces the synergistic relationship between α-synuclein aggregation and ferroptosis in Parkinson’s disease.

## Key findings

- α-synuclein aggregation directly induces ferroptosis and disrupts iron homeostasis.
- Iron accumulation accelerates α-synuclein fibrillation and oxidative stress, creating a harmful cycle.
- Glia cells amplify neurodegeneration by promoting inflammation and iron metabolism dysregulation.

## Abstract

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-synuclein (α-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-syn aggregation and ferroptosis. We detail how α-syn aggregation not only directly induces ferroptosis but also disrupts iron homeostasis, while iron accumulation in turn accelerates α-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-syn-ferroptosis axis, including α-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.