ArticleAging cell2023
Membrane phospholipid peroxidation promotes loss of dopaminergic neurons in psychological stress-induced Parkinson's disease susceptibility.
Article in Aging cell, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 1 of them a synthesis that pooled it.
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Who cites it
30 citing papers in PubMed, 1 synthesis or guideline pooled it, 41 citations in OpenAlex.
- Genome-wide association study provides insights into the genetic basis of Lewy body dementia.Molecular psychiatry · 2025Pooled it
- A Study on the Effects of Gluteal Muscle Activation on the Electromyography of Lower Limb Muscles in Young Male Patients With Patellofemoral Pain Syndrome.Orthopaedic surgery · 2025Trial
- Ferroptosis in major depressive disorder: Molecular mechanisms, cellular vulnerability, and therapeutic opportunities.Biochemistry and biophysics reports · 2026Review
- Catechol-Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Silencing arachidonate 15-lipoxygenase alleviates hypoxia-induced cognitive impairment through the mediation of phospholipase A2 group IVC-LPC18:0 to suppress ferroptosis.Molecular biomedicine · 2026Article
- Oleuropein Attenuates 6-Hydroxydopamine-Induced Cytotoxicity Through Redox Regulation in Differentiated Dopaminergic Neurons: Potential Involvement of RET-Associated Signalling.International journal of molecular sciences · 2026Article
- Spike RBD drives sustained Parkinson's disease progression via microglia-neuron crosstalk-mediated RTP801 upregulation.Journal of advanced research · 2026Article
- When Pathways Converge: Iron, Lipid Peroxidation, and α-Synuclein in Ferroptosis-Driven Dopaminergic Neurodegeneration.Journal of neurochemistry · 2026Review
- Luteolin Attenuates Asthma Via Inhibiting ALOX15 Mediated Bronchial Epithelial Cell Ferroptosis.Inflammation · 2026Article
- Ferroptosis in Myocardial Fibrosis: Mechanisms and Therapeutic Insights.Antioxidants (Basel, Switzerland) · 2026Review
- The Role of Lipid Metabolism in the Progression of Breast Cancer.Journal of Cancer · 2026Review
- Multi-Omics Analysis Reveals Distinct Lipid Remodelling and Mitochondrial Stress in SH-SY5Y Cells Modelling Parkinson's Disease.Metabolites · 2025Article
- Comprehensive review of leonurine: harnessing its therapeutic potential for chronic diseases.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Research progress on molecular mechanism and future perspectives of leonurine.Frontiers of medicine · 2025Review
- Lipid metabolism in health and disease: Mechanistic and therapeutic insights for Parkinson's disease.Chinese medical journal · 2025Review
- Psychological stress-activated NR3C1/NUPR1 axis promotes ovarian tumor metastasis.Acta pharmaceutica Sinica. B · 2025Article
- Chronic stress induces depression-like behaviors and Parkinsonism via upregulating α-synuclein.NPJ Parkinson's disease · 2025Article
- Oxidative Stress and Skin Diseases: The Role of Lipid Peroxidation.Antioxidants (Basel, Switzerland) · 2025Review
- "Weibing" in traditional Chinese medicine-biological basis and mathematical representation of disease-susceptible state.Acta pharmaceutica Sinica. B · 2025Review
- ALOX15-Mediated Neuron Ferroptosis Was Involved in Diabetic Peripheral Neuropathic Pain.CNS neuroscience & therapeutics · 2025Article
Corrections and comments
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Authors and funding
16 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Parkinson's disease (PD) is a neurodegenerative disorder associated with α-synuclein aggregation and dopaminergic neuron loss in the midbrain. There is evidence that psychological stress promotes PD progression by enhancing glucocorticoids-related oxidative damage, however, the mechanisms involved are unknown. The present study demonstrated that plasma membrane phospholipid peroxides, as determined by phospholipidomics, triggered ferroptosis in dopaminergic neurons, which in turn contributed to stress exacerbated PD-like motor disorder in mice overexpressing mutant human α-synuclein. Using hormonomics, we identified that stress stimulated corticosteroid release and promoted 15-lipoxygenase-1 (ALOX15)-mediated phospholipid peroxidation. ALOX15 was upregulated by α-synuclein overexpression and acted as a fundamental risk factor in the development of chronic stress-induced parkinsonism and neurodegeneration. Further, we demonstrated the mechanism by which corticosteroids activated the PKC pathway and induced phosphatidylethanolamine-binding protein-1 (PEBP1) to form a complex with ALOX15, thereby facilitating ALOX15 to locate on the plasma membrane phospholipids. A natural product isolated from herbs, leonurine, was screened with activities of inhibiting the ALOX15/PEBP1 interaction and thereby attenuating membrane phospholipid peroxidation. Collectively, our findings demonstrate that stress increases the susceptibility of PD by driving membrane lipid peroxidation of dopaminergic neurons and suggest the ALOX15/PEBP1 complex as a potential intervention target.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.