Iron(ing) out parkinsonisms: The interplay of proteinopathy and ferroptosis in Parkinson's disease and tau-related parkinsonisms
Parkinsonian syndromes are characterised by similar motor-related symptomology resulting from dopaminergic neuron damage. While Parkinson's disease (PD) is the most prevalent parkinsonism, we also focus on two other variants, Progressive supranuclear palsy (PSP) and Corticobasal degeneration (C...
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Elsevier
2025-02-01
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| Series: | Redox Biology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213231724004567 |
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| author | Maria João da Costa Caiado Amalia M. Dolga Wilfred F.A. den Dunnen |
| author_facet | Maria João da Costa Caiado Amalia M. Dolga Wilfred F.A. den Dunnen |
| author_sort | Maria João da Costa Caiado |
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| description | Parkinsonian syndromes are characterised by similar motor-related symptomology resulting from dopaminergic neuron damage. While Parkinson's disease (PD) is the most prevalent parkinsonism, we also focus on two other variants, Progressive supranuclear palsy (PSP) and Corticobasal degeneration (CBD). Due to the clinical similarities of these parkinsonisms, and since definite diagnoses are only possible post-mortem, effective therapies and novel biomarkers of disease are scarce. Thus, we explore the current findings relating to the relationship of parkinsonism proteinopathy (α-synuclein in PD, and tau in PSP/CBD) paralleled to a specific form of cell death, ferroptosis. Ferroptosis is characterised by iron-induced lipid peroxidation and several markers of this pathway have been identified to control intracellular iron fluctuations. However, in parkinsonism, these mechanisms are thought to become dysfunctional. Although both proteinopathies have been linked to ferroptosis, much less is known about ferroptotic cell death and tau in the context of PSP/CBD. Interestingly, clinical trials targeting iron have recently shown conflicting results which begs to question the complexity of the ferroptotic pathway and alludes to the need for exploring other ferroptosis-related machinery as possible therapeutic targets. Overall, we address the literature gap in parkinsonism proteinopathy and ferroptosis, and its relevance to understanding disease pathophysiology and aetiology. |
| format | Article |
| id | doaj-art-c70b95bd5ac54df98c7b82fb93463d54 |
| institution | Kabale University |
| issn | 2213-2317 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
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| series | Redox Biology |
| spelling | doaj-art-c70b95bd5ac54df98c7b82fb93463d542025-01-14T04:12:13ZengElsevierRedox Biology2213-23172025-02-0179103478Iron(ing) out parkinsonisms: The interplay of proteinopathy and ferroptosis in Parkinson's disease and tau-related parkinsonismsMaria João da Costa Caiado0Amalia M. Dolga1Wilfred F.A. den Dunnen2Graduate School of Medical Sciences (GSMS) and Research School of Behavioural and Cognitive Neurosciences (BCN), University of Groningen, 9713 GZ, Groningen, the Netherlands; Department of Pathology and Medical Biology, University Medical Centre Groningen (UMCG), Hanzeplein 1, 9713 GZ, Groningen, the Netherlands; Department of Molecular Pharmacology, Groningen Research Institute of Pharmacy (GRIP), University of Groningen, 9713 AV, Groningen, the Netherlands; Corresponding author. Graduate School of Medical Sciences (GSMS) and Research School of Behavioural and Cognitive Neurosciences (BCN), University of Groningen, 9713 GZ, Groningen, the Netherlands.Department of Pathology and Medical Biology, University Medical Centre Groningen (UMCG), Hanzeplein 1, 9713 GZ, Groningen, the Netherlands; Department of Molecular Pharmacology, Groningen Research Institute of Pharmacy (GRIP), University of Groningen, 9713 AV, Groningen, the NetherlandsDepartment of Pathology and Medical Biology, University Medical Centre Groningen (UMCG), Hanzeplein 1, 9713 GZ, Groningen, the NetherlandsParkinsonian syndromes are characterised by similar motor-related symptomology resulting from dopaminergic neuron damage. While Parkinson's disease (PD) is the most prevalent parkinsonism, we also focus on two other variants, Progressive supranuclear palsy (PSP) and Corticobasal degeneration (CBD). Due to the clinical similarities of these parkinsonisms, and since definite diagnoses are only possible post-mortem, effective therapies and novel biomarkers of disease are scarce. Thus, we explore the current findings relating to the relationship of parkinsonism proteinopathy (α-synuclein in PD, and tau in PSP/CBD) paralleled to a specific form of cell death, ferroptosis. Ferroptosis is characterised by iron-induced lipid peroxidation and several markers of this pathway have been identified to control intracellular iron fluctuations. However, in parkinsonism, these mechanisms are thought to become dysfunctional. Although both proteinopathies have been linked to ferroptosis, much less is known about ferroptotic cell death and tau in the context of PSP/CBD. Interestingly, clinical trials targeting iron have recently shown conflicting results which begs to question the complexity of the ferroptotic pathway and alludes to the need for exploring other ferroptosis-related machinery as possible therapeutic targets. Overall, we address the literature gap in parkinsonism proteinopathy and ferroptosis, and its relevance to understanding disease pathophysiology and aetiology.http://www.sciencedirect.com/science/article/pii/S2213231724004567Iron homeostasisSynucleinopathyTauopathyFerroptosisNeurodegenerationMitochondria |
| spellingShingle | Maria João da Costa Caiado Amalia M. Dolga Wilfred F.A. den Dunnen Iron(ing) out parkinsonisms: The interplay of proteinopathy and ferroptosis in Parkinson's disease and tau-related parkinsonisms Redox Biology Iron homeostasis Synucleinopathy Tauopathy Ferroptosis Neurodegeneration Mitochondria |
| title | Iron(ing) out parkinsonisms: The interplay of proteinopathy and ferroptosis in Parkinson's disease and tau-related parkinsonisms |
| title_full | Iron(ing) out parkinsonisms: The interplay of proteinopathy and ferroptosis in Parkinson's disease and tau-related parkinsonisms |
| title_fullStr | Iron(ing) out parkinsonisms: The interplay of proteinopathy and ferroptosis in Parkinson's disease and tau-related parkinsonisms |
| title_full_unstemmed | Iron(ing) out parkinsonisms: The interplay of proteinopathy and ferroptosis in Parkinson's disease and tau-related parkinsonisms |
| title_short | Iron(ing) out parkinsonisms: The interplay of proteinopathy and ferroptosis in Parkinson's disease and tau-related parkinsonisms |
| title_sort | iron ing out parkinsonisms the interplay of proteinopathy and ferroptosis in parkinson s disease and tau related parkinsonisms |
| topic | Iron homeostasis Synucleinopathy Tauopathy Ferroptosis Neurodegeneration Mitochondria |
| url | http://www.sciencedirect.com/science/article/pii/S2213231724004567 |
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