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Future Perspectives of Oxytosis/Ferroptosis Research in Neurodegeneration Diseases

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Abstract

The current report briefly summarizes the existing hypotheses and relevant evidence of oxytosis/ferroptosis-mediated cell death and outlines future perspectives of neurodegeneration research. Furthermore, it highlights the potential application of specific markers (e.g., activators, inhibitors, redox modulators, antioxidants, iron chelators) in the study of regulatory mechanisms of oxytosis/ferroptosis. It appears that these markers may be a suitable option for experimental investigations targeting key pathways of oxytosis/ferroptosis, such as the inhibition of the cystine/glutamate antiporter/glutathione/glutathione peroxidase 4 axis, glutamate oxidative toxicity, glutathione depletion, iron dyshomeostasis, iron-mediated lipid peroxidation, and others. From a clinical perspective, an innovative research approach to investigate the oxytosis/ferroptosis pathways in cells of the central nervous system and their relationship to neurodegenerative diseases is desirable. It is necessary to expand the existing knowledge about the molecular mechanisms of neurodegenerative diseases and to provide innovative diagnostic procedures to prevent their progression, as well as to develop effective neuroprotective treatment. The importance of preclinical studies focused predominantly on oxytosis/ferroptosis inhibitors (iron chelators or lipoxygenase inhibitors and lipophilic antioxidants) that could chelate iron or inhibit lipid peroxidation is also discussed. Specifically, this targeted inhibition of neuronal death could represent a potential therapeutic strategy for some neurodegenerative diseases.

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Data Availability

Data sharing does not applicable to this article as no datasets were generated or analyzed during the current study.

Abbreviations

CNS:

Central nervous system

Fer-1:

Ferrostatin-1

FINs:

Ferroptosis-inducing compound

FSP1:

Ferroptosis suppressor protein

GSH:

Glutathione

GPX4:

Glutathione peroxidase 4

Lip-1:

Liproxstatin

LPO:

Lipid peroxidation

LOX:

Lipoxygenase

PEBP1:

Phosphatidylethanolamine-binding protein 1

PUFAs:

Polyunsaturated fatty acids

ROS:

Reactive oxygen species

Xc¯:

Cystine/glutamate antiporter

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  1. Faculty of Medicine, Institute of Medical Chemistry, Biochemistry and Clinical Biochemistry, Comenius University in Bratislava, Sasinkova 2, 811 08, Bratislava, Slovakia

    Alena Viktorinova

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Viktorinova, A. Future Perspectives of Oxytosis/Ferroptosis Research in Neurodegeneration Diseases. Cell Mol Neurobiol 43, 2761–2768 (2023). https://doi.org/10.1007/s10571-023-01353-5

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