ArticleInternational journal of molecular sciences2023
The Relationship between Iron and LRRK2 in a 6-OHDA-Induced Parkinson's Disease Model.
Article in International journal of molecular sciences, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 9 citations in OpenAlex.
- Leucine-rich repeat kinase 2 (LRRK2): balancing cellular homeostasis and Parkinson's disease (PD) pathogenesis.Annals of medicine · 2026Review
- Synthetic Cyclic CAntioxidants (Basel, Switzerland) · 2026Article
- An LRRK2 variant blocks NCOA4 trafficking upon iron overload, leading to ferroptotic death.Journal of cell science · 2026Article
- Synthetic Cyclic CAntioxidants (Basel, Switzerland) · 2025Article
- From pathogenesis to treatment: the emerging role of ferroptosis in Parkinson's disease.Frontiers in immunology · 2025Review
- Unraveling Dysregulated Cell Signaling Pathways, Genetic and Epigenetic Mysteries of Parkinson's Disease.Molecular neurobiology · 2024Review
- Special Issue 'Advances in Neurodegenerative Diseases Research and Therapy 2.0'.International journal of molecular sciences · 2024Article
- Brain Iron Metabolism, Redox Balance and Neurological Diseases.Antioxidants (Basel, Switzerland) · 2023Review
- ACSL4-Mediated Ferroptosis and Its Potential Role in Central Nervous System Diseases and Injuries.International journal of molecular sciences · 2023Review
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Authors and funding
7 authors at 1 institution in 1 country.
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Abstract
The pathogenesis of Parkinson's disease (PD) is very complex and still needs further exploration. Leucine-rich repeat kinase 2 (LRRK2) is associated with familial PD in mutant forms and sporadic PD in the wild-type form. Abnormal iron accumulation is found in the substantia nigra of PD patients, but its exact effects are not very clear. Here, we show that iron dextran exacerbates the neurological deficit and loss of dopaminergic neurons in 6-OHDA lesioned rats. 6-OHDA and ferric ammonium citrate (FAC) significantly increase the activity of LRRK2 as reflected by the phosphorylation of LRRK2, at S935 and S1292 sites. 6-OHDA-induced LRRK2 phosphorylation is attenuated by the iron chelator deferoxamine, especially at the S1292 site. 6-OHDA and FAC markedly induce the expression of pro-apoptotic molecules and the production of ROS by activating LRRK2. Furthermore, G2019S-LRRK2 with high kinase activity showed the strongest absorptive capacity for ferrous iron and the highest intracellular iron content among WT-LRRK2, G2019S-LRRK2, and kinase-inactive D2017A-LRRK2 groups. Taken together, our results demonstrate that iron promotes the activation of LRRK2, and active LRRK2 accelerates ferrous iron uptake, suggesting that there exists an interplay between iron and LRRK2 in dopaminergic neurons, providing a new perspective to uncover the underlying mechanisms of PD occurrence.
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