Ferroptosis, a newly characterized form of cell death in Parkinson's disease that is regulated by PKC
Open accessAbstract
Parkinson's disease (PD) is a complex illness characterized by progressive dopaminergic neuronal loss. Several mechanisms associated with the iron-induced death of dopaminergic cells have been described. Ferroptosis is an iron-dependent, regulated cell death process that was recently described in cancer. Our present work show that ferroptosis is an important cell death pathway for dopaminergic neurons. Ferroptosis was characterized in Lund human mesencephalic cells and then confirmed ex vivo (in organotypic slice cultures) and in vivo (in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model). Some of the observed characteristics of ferroptosis differed from those reported previously. For example, ferroptosis may be initiated by PKCα activation, which then activates MEK in a RAS-independent manner. The present study is the first to emphasize the importance of ferroptosis dysregulation in PD. In neurodegenerative diseases like PD, iron chelators, Fer-1 derivatives and PKC inhibitors may be strong drug candidates to pharmacologically modulate the ferroptotic signaling cascade.
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A similar protective effect is observed in GPX4-independent models of renal ischemic or toxic injury, Parkinson disease, and other human pathologies.
“A similar protective effect is observed in GPX4-independent models of renal ischemic or toxic injury [540, 592], Parkinson disease [593], and other human pathologies [594].”
From Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018. (2018) · cites this paper as [593]
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Self-citation
- Authors
- Do Van, B., Gouel, F., Jonneaux, A., Timmerman, K., Gelé, P., Pétrault, M., Bastide, M., Laloux, C., Moreau, C., Bordet, R., Devos, D., & Devedjian, J.-C.
- Affiliations
- Inserm (FR)
- Centre Hospitalier Universitaire de Lille (FR)
- Université Lille Nord de France (FR)
- Corresponding author
- Devedjian, Jean-Christophe
- ORCID
- Venue
- Neurobiology of Disease
- Publisher
- Elsevier BV
- Published
- 2016-10
- Volume
- 94
- Pages
- 169-178
- ISSN
- 0969-9961 (ISSN-L)
- OpenAlex
- W2374069442
- Cited by
- 689
- References
- 36
- Citations by year
- 2026: 48 · 2025: 73 · 2024: 89 · 2023: 109 · 2022: 117 · 2021: 81 · 2020: 80 · 2019: 41 · 2018: 30 · 2017: 17 · 2016: 3
- FWCI
- 22.81
- Type
- journal article
- Language
- en
- Open access
- green
- doaj.org
- Licence
- Locations
- Neurobiology of Disease (publishedVersion)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- French Ministry of Health (2008-006842-25, DN2M2015)
- DN2M regional grant
- French Parkinson's Disease Association
- Topics
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Ferroptosis and cancer prognosis
- Life Sciences › Neuroscience › Neurology › Neurological diseases and metabolism
- Keywords
- ferroptosis, Parkinson's disease, protein kinase C alpha, MEK activation, Ras-independent signaling, dopaminergic neurons, iron-dependent cell death, organotypic slice cultures, iron chelators, PKC inhibitors, neurodegeneration
- MeSH terms
- Animals, Dopamine, Humans, Iron, Mesencephalon, Parkinson Disease, Protein Kinase C, Substantia Nigra, Signal Transduction, Cell Death, Rats, Sprague-Dawley, Apoptosis, Dopaminergic Neurons
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