ArticleScientific reports2011
Mechanism of copper(II)-induced misfolding of Parkinson's disease protein.
Article in Scientific reports, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 83 citations in OpenAlex.
- Cuproptosis: New Mechanisms Linking Endothelial Dysfunction to Neurodegenerative Diseases and Therapeutic Prospects.International journal of molecular sciences · 2026Review
- Perturbations in levels of essential metals less severe in Parkinson's disease without dementia than in Parkinson's disease dementia.Metallomics : integrated biometal science · 2025Article
- Copper homeostasis and pregnancy complications: a comprehensive review.Journal of assisted reproduction and genetics · 2025Review
- Primary Nucleation of Polymorphic α-Synuclein Dimers Depends on Copper Concentrations and Definite Copper-Binding Site.Biomolecules · 2024Article
- Targeting cuproplasia and cuproptosis in cancer.Nature reviews. Clinical oncology · 2024Review
- Copper homeostasis and the ubiquitin proteasome system.Metallomics : integrated biometal science · 2023Review
- Machine learning screening for Parkinson's disease-related cuproptosis-related typing development and validation and exploration of personalized drugs for cuproptosis genes.Annals of translational medicine · 2023Article
- Microglial Activation in Metal Neurotoxicity: Impact in Neurodegenerative Diseases.BioMed research international · 2023Review
- Multiparametric High-Content Cell Painting Identifies Copper Ionophores as Selective Modulators of Esophageal Cancer Phenotypes.ACS chemical biology · 2022Article
- Ceruloplasmin Deamidation in Neurodegeneration: From Loss to Gain of Function.International journal of molecular sciences · 2021Review
- Review
- Copper Toxicity Links to Pathogenesis of Alzheimer's Disease and Therapeutics Approaches.International journal of molecular sciences · 2020Review
- Subcellular Localization of Copper-Cellular Bioimaging with Focus on Neurological Disorders.International journal of molecular sciences · 2020Review
- Metal Toxicity Links to Alzheimer's Disease and Neuroinflammation.Journal of molecular biology · 2019Review
- Parkinson's Disease and the Environment.Frontiers in neurology · 2019Review
- Tuning the Balance between Fibrillation and Oligomerization of α-Synuclein in the Presence of Dopamine.ACS omega · 2018Article
- Dexamethasone Inhibits Copper-Induced Alpha-Synuclein Aggregation by a Metallothionein-Dependent Mechanism.Neurotoxicity research · 2018Article
- Article
- Metallothionein, Copper and Alpha-Synuclein in Alpha-Synucleinopathies.Frontiers in neuroscience · 2017Review
- Copper(II) and the pathological H50Q α-synuclein mutant: Environment meets genetics.Communicative & integrative biology · 2017Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
α-synuclein (aS) is a natively unfolded pre-synaptic protein found in all Parkinson's disease patients as the major component of fibrillar plaques. Metal ions, and especially Cu(II), have been demonstrated to accelerate aggregation of aS into fibrillar plaques, the precursors to Lewy bodies. In this work, copper binding to aS is investigated by a combination of quantum and molecular mechanics simulations. Starting from the experimentally observed attachment site, several optimized structures of Cu-binding geometries are examined. The most energetically favorable attachment results in significant allosteric changes, making aS more susceptible to misfolding. Indeed, an inverse kinematics investigation of the configuration space uncovers a dynamically stable β-sheet conformation of Cu-aS that serves as a nucleation point for a second β-strand. Based on these findings, we propose an atomistic mechanism of copper-induced misfolding of aS as an initial event in the formation of Lewy bodies and thus in PD pathogenesis.
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