ArticleNeurobiology of disease2015
Effects of impaired membrane interactions on α-synuclein aggregation and neurotoxicity.
Article in Neurobiology of disease, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers, 1 of them a synthesis that pooled it.
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Who cites it
58 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Emerging links between pediatric lysosomal storage diseases and adult parkinsonism.Movement disorders : official journal of the Movement Disorder Society · 2019Pooled it
- Dual effect of α-synuclein disease variants on condensate formation.Nature communications · 2026Article
- Cis-Acting Chaperoning by Macromolecular Tethering: A Built-In Layer of Cellular Chaperoning.International journal of molecular sciences · 2026Review
- Multi-parameter fluorescence lifetime imaging for high-noise neuroscience applications.Biomedical optics express · 2026Article
- Lipid packing defects are necessary and sufficient for membrane binding of α-synuclein.Communications biology · 2025Article
- Phosphoproteome modifications and cortical circuit dysfunction are linked to the early-stage progression of alpha-synuclein aggregation.bioRxiv : the preprint server for biology · 2025Article
- Mechanisms of Alpha-Synuclein-Seeded Aggregation in Neurons Revealed by Fluorescence Lifetime Imaging.ACS chemical neuroscience · 2025Article
- Lipid Packing Defects are Necessary and Sufficient for Membrane Binding of α-Synuclein.bioRxiv : the preprint server for biology · 2025Article
- Glycine-to-aspartic acid mutation at codon 51 inBrain communications · 2025Article
- Epigenetic Explorations of Neurological Disorders, the Identification Methods, and Therapeutic Avenues.International journal of molecular sciences · 2024Review
- Research Priorities on the Role of α-Synuclein in Parkinson's Disease Pathogenesis.Movement disorders : official journal of the Movement Disorder Society · 2024Review
- Tubulin-binding region alters tau-lipid interactions and changes toxicity of tau fibrils formed in the presence of phosphatidylserine lipids.Protein science : a publication of the Protein Society · 2024Article
- Parkinson's disease-associated mutations in α-synuclein alters its lipid-bound state.Biophysical journal · 2024Article
- Secondary structure and toxicity of lysozyme fibrils are determined by the length and unsaturation of phosphatidic acid.Proteins · 2024Article
- Generation of G51D and 3D mice reveals decreased α-synuclein tetramer-monomer ratios promote Parkinson's disease phenotypes.NPJ Parkinson's disease · 2024Article
- Protective Effects of Polyphenol-Rich Extracts against Neurotoxicity Elicited by Paraquat or Rotenone in Cellular Models of Parkinson's Disease.Antioxidants (Basel, Switzerland) · 2023Article
- Protein kinase R dependent phosphorylation of α-synuclein regulates its membrane binding and aggregation.PNAS nexus · 2022Article
- Threonine Cavities Are Targetable Motifs That Control Alpha-Synuclein Fibril Growth.ACS chemical neuroscience · 2022Article
- Phosphatidylcholine and Phosphatidylserine Uniquely Modify the Secondary Structure of α-Synuclein Oligomers Formed in Their Presence at the Early Stages of Protein Aggregation.ACS chemical neuroscience · 2022Article
- Aromaticity at position 39 in α-synuclein: A modulator of amyloid fibril assembly and membrane-bound conformations.Protein science : a publication of the Protein Society · 2022Article
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9 authors.
Funding
Abstract
The post-mortem brains of individuals with Parkinson's disease (PD) and other synucleinopathy disorders are characterized by the presence of aggregated forms of the presynaptic protein α-synuclein (aSyn). Understanding the molecular mechanism of aSyn aggregation is essential for the development of neuroprotective strategies to treat these diseases. In this study, we examined how interactions between aSyn and phospholipid vesicles influence the protein's aggregation and toxicity to dopaminergic neurons. Two-dimensional NMR data revealed that two familial aSyn mutants, A30P and G51D, populated an exposed, membrane-bound conformer in which the central hydrophobic region was dissociated from the bilayer to a greater extent than in the case of wild-type aSyn. A30P and G51D had a greater propensity to undergo membrane-induced aggregation and elicited greater toxicity to primary dopaminergic neurons compared to the wild-type protein. In contrast, the non-familial aSyn mutant A29E exhibited a weak propensity to aggregate in the presence of phospholipid vesicles or to elicit neurotoxicity, despite adopting a relatively exposed membrane-bound conformation. Our findings suggest that the aggregation of exposed, membrane-bound aSyn conformers plays a key role in the protein's neurotoxicity in PD and other synucleinopathy disorders.
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