Efficacy of the iron‐chelating agent, deferiprone, in patients with Parkinson's disease: A systematic review and meta‐analysis

Negida, Ahmed; Hassan, Nafisa M.; Aboeldahab, Heba; Zain, Youmna E.; Negida, Yasmin; Cadri, Shirin; Cadri, Nivin; Cloud, Leslie J.; Barrett, Matthew J.; Berman, Brian

doi:10.1111/cns.14607

Cited by 7 publications

(1 citation statement)

References 36 publications

(62 reference statements)

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“…Currently, therapeutic studies targeting ferroptosis in PD have focused on the use of drugs such as iron chelators, antioxidants, and autophagy activators. For instance, iron chelators like deferoxamine have been shown to reduce iron deposition in SN of PD patients, thereby mitigating the progression of motor disorders ( Negida et al, 2024 ). Antioxidants targeting ferroptosis, including N-Acetylcysteine (NAC), Vitamin E, Coenzyme Q10, ACSL4 inhibitors, LOX inhibitors, GPX4 activators, and Nrf2 activators, have also shown potential in slowing PD progression in the study.…”

Section: Discussionmentioning

confidence: 99%

Research trends of ferroptosis and pyroptosis in Parkinson’s disease: a bibliometric analysis

Wu,

Zhong,

Tang

et al. 2024

Front. Mol. Neurosci.

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ObjectiveThis study aims to visualize the trends and hotspots in the research of “ferroptosis in PD” and “pyroptosis in PD” through bibliometric analysis from the past to 2024.MethodsLiterature was retrieved from the Web of Science Core Collection (WoSCC) from the past to February 16, 2024, and bibliometric analysis was conducted using Vosviewer and Citespace.Results283 and 542 papers were collected in the field of “ferroptosis in PD” and “pyroptosis in PD.” The number of publications in both fields has increased yearly, especially in “ferroptosis in PD,” which will become the focus of PD research. China, the United States and England had extensive exchanges and collaborations in both fields, and more than 60% of the top 10 institutions were from China. In the fields of “ferroptosis in PD” and “pyroptosis in PD,” the University of Melbourne and Nanjing Medical University stood out in terms of publication numbers, citation frequency, and centrality, and the most influential journals were Cell and Nature, respectively. The keyword time zone map showed that molecular mechanisms and neurons were the research hotspots of “ferroptosis in PD” in 2023, while memory and receptor 2 were the research hotspots of “pyroptosis in PD” in 2023, which may predict the future research direction.ConclusionThis study provides insights into the development, collaborations, research themes, hotspots, and tendencies of “ferroptosis in PD” and “pyroptosis in PD.” Overall situation of these fields is available for researchers to further explore the underlying mechanisms and potential treatments.

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Section: Discussionmentioning

confidence: 99%

Research trends of ferroptosis and pyroptosis in Parkinson’s disease: a bibliometric analysis

Wu,

Zhong,

Tang

et al. 2024

Front. Mol. Neurosci.

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ATH434, a promising iron-targeting compound for treating iron regulation disorders

Pall,

Bond,

Bailey

et al. 2024

Metallomics

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Cytotoxic accumulation of loosely bound mitochondrial Fe2+ is a hallmark of Friedreich's Ataxia (FA), a rare and fatal neuromuscular disorder with limited therapeutic options. There are no clinically approved medications targeting excess Fe2+ associated with FA or the neurological disorders Parkinson's disease and Multiple System Atrophy. Traditional iron-chelating drugs clinically approved for systemic iron overload that target ferritin-stored Fe3+ for urinary excretion demonstrated limited efficacy in FA and exacerbated ataxia. Poor treatment outcomes reflect inadequate binding to excess toxic Fe2+ or exceptionally high affinities (i.e. ≤10−31) for non-pathologic Fe3+ that disrupts intrinsic iron homeostasis. To understand previous treatment failures and identify beneficial factors for Fe2+-targeted therapeutics, we compared traditional Fe3+ chelators deferiprone (DFP) and deferasirox (DFX) with additional iron-binding compounds including ATH434, DMOG, and IOX3. ATH434 and DFX had moderate Fe2+ binding affinities (Kd’s of 1–4 µM), similar to endogenous iron chaperones, while the remaining had weaker divalent metal interactions. These compounds had low/moderate affinities for Fe3+(0.46–9.59 µM) relative to DFX and DFP. While all compounds coordinated iron using molecular oxygen and/or nitrogen ligands, thermodynamic analyses suggest ATH434 completes Fe2+ coordination using H2O. ATH434 significantly stabilized bound Fe2+ from ligand-induced autooxidation, reducing reactive oxygen species (ROS) production, whereas DFP and DFX promoted production. The comparable affinity of ATH434 for Fe2+ and Fe3+ position it to sequester excess Fe2+ and facilitate drug-to-protein iron metal exchange, mimicking natural endogenous iron binding proteins, at a reduced risk of autooxidation-induced ROS generation or perturbation of cellular iron stores.

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Subcortical imaging-derived phenotypes are associated with the risk of Parkinson’s disease: A Mendelian Randomization Study

Chen,

Liu,

You

2024

Preprint

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Background The abnormalities of subcortical structures, such as putamen and caudate, play a key role in the occurrence of Parkinson's disease (PD); however, whether and how imaging-derived phenotypes (IDPs) in subcortical structures are causally associated with the risk of PD remain poorly understood. Methods The causal associations between subcortical IDPs from UK biobank and risk of PD were evaluated with bidirectional two-sample Mendelian randomization (MR) studies. Results Totally five subcortical IDPs were found to be causally associated with the risk of PD. Among these IDPs, IDP 168 (Global volume of subcortical gray matter, OR = 1.38 [1.16, 1.63], P = 1.82 x 10-4), IDP 214 (Right putamen volume, OR = 1.31 [1.15, 1.50], P = 7.71 x 10-5) and IDP 1441 (T2* signal in right caudate, OR = 1.21 [1.09, 1.35], P = 5.23 x 10-4) were found to be associated with increased risk of PD. In contrast, IDP 1358 (Mean intensity in right caudate, OR = 0.72 [0.62, 0.85), P = 6.77 x 10-5) and IDP 1344 (Mean intensity in left caudate, OR = 0.76 [0.65, 0.88], P = 3.23 x 10-4) were associated with reduced risk of PD. Conclusions The specific imaging features of the caudate and putamen are causally associated with altered risk of developing PD, thereby providing new insights into the development of novel predictive imaging biomarkers and therapies for PD patients.

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Efficacy of the iron‐chelating agent, deferiprone, in patients with Parkinson's disease: A systematic review and meta‐analysis

Cited by 7 publications

References 36 publications

Research trends of ferroptosis and pyroptosis in Parkinson’s disease: a bibliometric analysis

Research trends of ferroptosis and pyroptosis in Parkinson’s disease: a bibliometric analysis

ATH434, a promising iron-targeting compound for treating iron regulation disorders

Subcortical imaging-derived phenotypes are associated with the risk of Parkinson’s disease: A Mendelian Randomization Study

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